A Review of Traditional Applications, Geographic Distribution, Botanical Characterization, Phytochemistry, and Pharmacology of Hypericum ascyron L.

Abstract

Hypericum ascyron L. (H. ascyron) is a significant medicinal plant traditionally used for various conditions like hematemesis, hemoptysis, injuries from falls, irregular menses, dysmenorrhea, and liver fire-induced headaches. A comprehensive literature search was conducted using databases like SciFinder and Web of Science to explore its traditional uses, geographical distribution, botanical description, phytochemistry, and pharmacology. The objective of this review is to lay groundwork and suggest fresh avenues of investigation into the possible uses of the plant. Currently, two hundred and seventy compounds have been isolated and identified from H. ascyron, including phloroglucinols, xanthones, flavonoids, phenolics, steroids and triterpenoids, volatile components, and other compounds. Notably, phloroglucinols, xanthones, and flavonoids have exhibited remarkable pharmacological effects like antioxidant, antidiabetic, anti-inflammatory, antidepressant, cytotoxic, and antimicrobial activities. Despite extensive research, further studies are needed to understand new components and mechanisms of action, requiring more detailed investigations. This thorough exploration could facilitate the advancement and utilization of H. ascyron.

1. Introduction

Hypericum ascyron L. (H. ascyron), as shown in Figure 1, is an herbaceous plant of the Guttiferae family, belonging to the genus Hypericum. It has a long history of use in traditional Chinese medicine. Studies investigating the phytochemical composition of this plant have identified phloroglucinols [1,2,3,4,5,6,7,8,9,10,11] as its predominant secondary metabolites, a class of natural products with diverse biological activities. In addition to phloroglucinols, xanthones [11,12,13,14], flavonoids [15,16,17,18], phenolics [14,18,19], steroids or triterpenoids [20,21,22], and volatile components [13,23,24] have also been reported in H. ascyron.

Recent research has unveiled a multitude of pharmacological activities associated with H. ascyron, including antihistamine properties [25], analgesic and anti-inflammatory effects [26,27], antioxidant activity [28,29,30], α-glucosidase inhibition, antidiabetic effects [29,30], antibacterial properties [15,31], anti-HIV activity [2,32], antitumor effects [9,33], antidepressant and neuroprotective activity [5,8,34], hepatoprotective effects [5], and inhibition of tyrosinase and xanthine oxidase [35,36]. Despite these findings, there is currently no comprehensive review regarding the traditional uses, geographic distribution, botanical description, phytochemistry, and pharmacology of H. ascyron. Our review aims to bridge this gap by detailing two hundred and seventy constituents, including their names, formulas, chemical structures, theoretical molecular weights, sources, and characterization methods. Furthermore, our review provides an exhaustive classification of pharmacological research, incorporating the latest discoveries on H. ascyron to present a current and thorough perspective. Additionally, we offer an in-depth overview of traditional uses, geographic distribution, and botanical description. This review is intended to serve as a valuable resource for future studies on H. ascyron, offering novel perspectives on the judicious exploitation of H. ascyron resources and the effective creation of associated offerings.

2. Materials and Methods

To guarantee the trustworthiness and completeness of the data collected for this review, a thorough data collection process was undertaken from various databases, including SciFinder, Web of Science, PubMed, ProQuest, and CNKI. The search encompassed articles from peer-reviewed journals, Ph.D. and master’s theses, conference papers, and seminal works on Chinese herbal medicines. Specific keywords such as phytochemistry, phloroglucinols, geographical distribution, pharmacology, biological activity, antioxidant, anti-inflammatory, cytotoxicity, and other pertinent terms were utilized in conjunction with H. ascyron to broaden the research scope. This method enabled the retrieval of a comprehensive array of relevant studies published between 1970 and February 2024.

3. Traditional Applications

The pharmacological properties of H. ascyron have been acknowledged for centuries, with early mentions in ancient Chinese medicinal texts such as the “Newly Revised Material Medica” (Xinxiu Bencao) and the “Compendium of Material Medica” (Bencao Gangmu) [37]. The whole plant of H. ascyron is utilized in medicine, characterized by a bitter and cold nature, associated with the liver meridian, and considered non-toxic. Its primary functions include calming the liver, cooling blood to stop bleeding, clearing heat and toxicity, and expelling wind-damp. It is predominantly employed in addressing conditions like hematemesis, hemoptysis, epistaxis, hematuria, metrorrhagia, injuries from falls, external and internal bleeding, irregular menses, dysmenorrhea, breast milk stoppage, liver fire-induced headaches, jaundice, malaria, burns, sores, furuncles, eczema, impetigo, snakebites, rheumatism, and dysentery. Additionally, soaking the seeds in Chinese Baijiu can aid in treating stomach ailments, detoxifying, and promoting pus drainage [38,39]. Various specific prescriptions involving H. ascyron include the following: (1) For malaria treatment, boil seven flowers of H. ascyron in water and consume the decoction. (2) To address conditions like headaches due to liver fire, hematemesis, hemoptysis, epistaxis, and uterine bleeding, it is recommended to decoct 4.5–9 g of H. ascyron with water for oral consumption. (3) For injuries from falls, sores, and furuncles, applying crushed H. ascyron externally or utilizing its juice on the affected area is advised [38].

4. Geographical Distribution

H. ascyron is widely distributed across most parts of China except for Xinjiang, Qinghai, and Hainan. Figure 2 illustrates the general geographical distribution of L. bulbifera in China. Additionally, it is found in regions of Russia (Altai to Kamchatka and Sakhalin Island), North Korea, Japan, northern Vietnam, northeastern United States, and Canada. It typically thrives under various conditions such as mountain slopes, forest edges, grasslands, meadows, streams, and riverbanks at altitudes ranging from 0 to 2800 m. Furthermore, it is commonly cultivated in gardens [39,40].

5. Botanical Description

H. ascyron is a perennial herb that typically grows to a height of 0.5–1.3 m. It has an erect or occasionally ascending posture from a short creeping base. The stems are usually single or a few, forming tufts, unbranched, or branching at the upper part, sometimes emitting small branches from the leaf axils. When young, the stems are 4-angled, transitioning to 4-lined or occasionally 2-lined internodes below. The leaves are opposite, sessile, and have lanceolate, oblong-lanceolate, or oblong-ovate to elliptical shapes, or narrow oblongs. They measure 4–10 cm in length and 1–3 cm in width, with a gradually pointed, acute, or obtuse apex. The base is wedge-shaped or heart-shaped with a stem, and the edges are entire, thickly papery, green on top, and usually light green with scattered light-colored glandular dots below. The midrib, lateral vein, and veins near the edge are distinct underneath, with a dense vein network. The inflorescence bears 1–35 flowers, terminal, nearly corymbose to narrowly conical. The flowers have a diameter of 3–8 cm, flat or outward-curved. The flower bud is ovoid, with a rounded or blunt apex, and the pedicel measures 0.5–3 cm in length. The sepals are ovate or lanceolate to elliptical or oblong, 5–15 mm long and 1.5–7 mm wide, acute to obtuse at the apex, entire, and upright when fruiting. The petals are golden yellow, oblanceolate, 1.5–4 cm long and 0.5–2 cm wide, highly curved, and may or may not have glandular spots, remaining persistent. The stamens are extremely numerous, organized into 5 bundles, each containing around 30 stamens. The anthers are golden yellow with pine-like glandular dots. The ovary is broadly ovoid to narrowly ovoid triangular, 4–7 mm long, 5-loculed, with a central cavity; the style is 5 and ranges from 1/2 to twice the length of the ovary, detached from the base or up to 4/5 of the upper part. The capsule can be broad or narrow, shaped like an ovoid or ovoid triangle, measuring 0.9–2.2 cm in length and 0.5–1.2 cm in width. The mature capsule is brown with a 5-lobed apex. The stigma often appears folded. The seeds are dark red-brown to yellow-brown, cylindrical, slightly curved, 1–1.5 mm long, deeply carinate, or narrowly winged, occasionally with a slight terminal expansion; the testa is densely and shallowly linear-reticulate. H. ascyron blooms from July to August and fruits from August to September [39,40].

6. Phytochemistry

Recently, there has been increasing curiosity in investigating the bioactive ingredients extracted from different sections of H. ascyron, such as the aerial parts, roots, and entire plant. This surge in attention towards the components of this plant corresponds with the increasing recognition of its importance and potential applications. Recent reports indicate the isolation and identification of a total of two hundred and seventy compounds from H. ascyron, which are broadly classified into seven groups: phloroglucinols, xanthones, flavonoids, phenolics, steroids and triterpenoids, volatile components, and other compounds. The extensive variety of bioactive ingredients present in H. ascyron underscores its significance as a valuable resource for drug development and potential clinical uses.

6.1. Phloroglucinols

Phloroglucinols represent a significant class of natural compounds with widespread occurrence in the genus Hypericum. Notably, phloroglucinols exhibit a remarkable structural diversity due to potential oligomerization and conjugation with units from different biosynthetic pathways [41]. These compounds typically feature diverse chemical structures with side chains bearing various functional groups like acyl, hydroxyl, prenyl, and geranyl. The iterative cellular processes involved in their synthesis lead to the formation of complex ring systems with rearranged prenyl and geranyl groups. Currently, H. ascyron has isolated ninety-five distinct phloroglucinols (1–95) (

Table 1. Phloroglucinols isolated or identified from Hypericum ascyron L.

No.	Name	Formula	Exact Theoretical Molecular Weight	Source	Characterization Method	Ref.
1.	Ascyrone A	C34H44O6	548.3138	aerial parts	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, ROESY, HMBC, CD	[8]
2.	Ascyrone B	C34H44O7	564.3087	aerial parts	${\left[\alpha \right]}_D^{20}$, UV, HRESIMS, 1H NMR, 13C NMR, ROESY, HSQC, HMBC, CD	[8]
3.	Ascyrone C	C34H44O6	548.3138	aerial parts	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, HMBC, ROESY, CD	[8]
4.	Ascyrone D	C34H44O6	548.3138	aerial parts	${\left[\alpha \right]}_D^{20}$, UV, HRESIMS, 1H NMR, 13C NMR, ROESY, CD	[8]
5.	Ascyrone E	C34H42O5	530.3032	aerial parts	${\left[\alpha \right]}_D^{20}$, UV, HRESIMS, 1H NMR, 13C NMR, HMBC, ROESY, CD	[8]
6.	Longistylione A	C34H44O5	532.3189	roots	HRESIMS, 1H NMR, 13C NMR	[4]
				aerial parts	1D NMR, 2D NMR, CD	[34]
7.	Longistylione B	C34H44O5	532.3189	aerial parts	1H NMR, 13C NMR, CD	[8]
				roots	HRESIMS, 1H NMR, 13C NMR	[4]
				aerial parts	1D NMR, 2D NMR, CD	[34]
8.	Longistylione C	C34H44O5	532.3189	aerial parts	1H NMR, 13C NMR, CD	[8]
				roots	HRESIMS, 1H NMR, 13C NMR	[4]
				aerial parts	1D NMR, 2D NMR, CD	[34]
9.	Longistylione D	C34H44O5	532.3189	aerial parts	1H NMR, 13C NMR, CD	[8]
				roots	HRESIMS, 1H NMR, 13C NMR	[4]
				aerial parts	1D NMR, 2D NMR, CD	[34]
10.	Hyperascyrin N	C34H44O6	548.3138	aerial parts	1H NMR, 13C NMR, CD	[8]
11.	Hypascyrin A	C31H46O5	498.3345	roots	${\left[\alpha \right]}_D^{25}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, HMBC, NOESY, CD	[7]
12.	Hypascyrin B	C30H44O5	484.3189	roots	${\left[\alpha \right]}_D^{23}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, CD	[7]
13.	Hypascyrin C	C31H46O5	498.3345	roots	${\left[\alpha \right]}_D^{25}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, CD	[7]
14.	Hypascyrin D	C31H48O6	516.3451	roots	${\left[\alpha \right]}_D^{26}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, HMBC, NOESY, CD	[7]
15.	Hypascyrin E	C31H46O5	498.3345	roots	${\left[\alpha \right]}_D^{21}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, HMBC, NOESY, CD	[7]
16.	ent-Hyphenrone J	C30H44O5	484.3189	roots	${\left[\alpha \right]}_D^{21}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, CD	[7]
17.	Hyphenrone K	C31H46O5	498.3345	roots	${\left[\alpha \right]}_D^{22}$, 1H NMR, 13C NMR, CD	[7]
18.	Hypercalin B	C33H42O5	518.3032	aerial parts	1H NMR, 13C NMR	[1]
				whole plant	mp, EI-MS, 1H NMR, 13C NMR	[42]
19.	Hypercalin C	C30H44O5	484.3189	roots	1H NMR, 13C NMR	[7]
				aerial parts	1H NMR, 13C NMR	[1]
				whole plant	mp, EI-MS, 1H NMR, 13C NMR	[42]
20.	3,5-Dihydroxy-4-{[(1R,2S,5S)-2-hydroxy-2-methyl-5-(1-methylethenyl)cyclopentyl]methyl}-2-(3-methylbutanoyl)-6,6-bis(3-methylbut-2-enyl)cyclohexa-2,4-dien-1-one	C31H46O5	498.3345	aerial parts	1H NMR, 13C NMR	[1]
21.	Tomoeone A	C30H44O6	500.3138	roots	1H NMR, 13C NMR	[7]
				aerial parts	1H NMR, 13C NMR	[2]
				aerial parts	${\left[\alpha \right]}_D$, IR, HRESIMS, 1H NMR, 13C NMR, COSY, HSQC, HMBC, NOESY	[1]
				aerial parts	ESI-MS, 1H NMR, 13C NMR	[9]
				aerial parts	UV, HRESIMS, 1H NMR, 13C NMR, HMBC, NOESY	[11]
22.	Tomoeone B	C30H44O6	500.3138	aerial parts	1H NMR, 13C NMR, CD	[2]
				aerial parts	${\left[\alpha \right]}_D$, IR, HRESIMS, 1H NMR, 13C NMR, COSY, HSQC, HMBC, NOESY	[1]
				aerial parts	ESI-MS, 1H NMR, 13C NMR	[9]
23.	Tomoeone C	C30H44O6	500.3138	aerial parts	${\left[\alpha \right]}_D$, IR, HRESIMS, 1H NMR, 13C NMR, COSY, HSQC, HMBC, NOESY	[1]
24.	Revised tomoeone C	C30H44O7	516.3087	aerial parts	ESI-MS, 1H NMR, 13C NMR	[9]
25.	Tomoeone D	C30H44O6	500.3138	aerial parts	${\left[\alpha \right]}_D$, IR, HRESIMS, 1H NMR, 13C NMR, COSY, HSQC, HMBC, NOESY	[1]
26.	Tomoeone E	C31H46O6	514.3294	aerial parts	1H NMR, 13C NMR, CD	[2]
				aerial parts	${\left[\alpha \right]}_D$, IR, HRESIMS, 1H NMR, 13C NMR, COSY, HSQC, HMBC, NOESY	[1]
				aerial parts	ESI-MS, 1H NMR, 13C NMR	[9]
27.	Tomoeone F	C31H46O6	514.3294	aerial parts	1H NMR, 13C NMR, CD	[2]
				aerial parts	${\left[\alpha \right]}_D$, IR, HRESIMS, 1H NMR, 13C NMR, COSY, HSQC, HMBC, NOESY	[1]
28.	Tomoeone G	C31H46O6	514.3294	aerial parts	${\left[\alpha \right]}_D$, IR, HRESIMS, 1H NMR, 13C NMR, COSY, HSQC, HMBC, NOESY	[1]
29.	Revised tomoeone G	C31H46O7	530.3244	aerial parts	1H NMR, 13C NMR, CD	[2]
				aerial parts	ESI-MS, 1H NMR, 13C NMR	[9]
30.	Tomoeone H	C31H46O7	530.3244	roots	1H NMR, 13C NMR	[7]
				aerial parts	${\left[\alpha \right]}_D$, IR, HRESIMS, 1H NMR, 13C NMR, COSY, HSQC, HMBC, NOESY	[1]
				aerial parts	1H NMR, 13C NMR, CD	[2]
31.	Hyperascyrin A	C34H44O5	532.3189	roots	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, HSQC, HMBC, NOESY, CD	[4]
32.	Hyperascyrin B	C34H44O5	532.3189	roots	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, NOESY, CD	[4]
33.	Hyperascyrin C	C34H44O6	548.3138	roots	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, HMBC, NOESY, CD	[4]
34.	Hyperascyrin D	C34H44O6	548.3138	roots	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, NOESY, CD	[4]
35.	Hyperascyrin E	C34H44O5	532.3189	roots	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, HMBC, NOESY, CD	[4]
36.	Hyperascyrin F	C34H44O5	532.3189	roots	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, HMBC, NOESY, CD	[4]
37.	Hyperascyrin G	C34H44O6	548.3138	roots	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, NOESY, CD	[4]
38.	Hyperascyrin H	C34H44O6	548.3138	roots	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, NOESY, CD	[4]
39.	Hyperascyrin I	C34H44O6	548.3138	roots	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, NOESY, CD	[4]
40.	Hyperascyrin J	C34H44O5	532.3189	roots	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, HMBC, NOESY, CD	[4]
41.	Hyperascyrin K	C34H44O5	532.3189	roots	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, HMBC, NOESY, CD	[4]
42.	Hyperascyrone A	C33H42O6	534.2981	aerial parts	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, DEPT, 1H-1H COSY, NOESY, HMBC, CD	[2]
43.	Hyperascyrone B	C30H44O6	500.3138	aerial parts	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, NOESY, HMBC, CD	[2]
44.	Hyperascyrone C	C31H46O6	514.3294	aerial parts	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, NOESY, HMBC, CD	[2]
45.	Hyperascyrone D	C30H44O6	500.3138	aerial parts	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, NOESY, HMBC, CD	[2]
				aerial parts	ESI-MS, 1H NMR, 13C NMR	[9]
46.	Hyperascyrone E	C31H46O6	514.3294	aerial parts	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, NOESY, HMBC, CD	[2]
				aerial parts	ESI-MS, 1H NMR, 13C NMR	[9]
47.	Hyperascyrone F	C31H46O6	514.3294	aerial parts	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, NOESY, HMBC, CD	[2]
48.	Hyperascyrone G	C31H46O6	514.3294	aerial parts	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, NOESY, HMBC, CD	[2]
49.	Hyperascyrone H	C31H46O6	514.3294	aerial parts	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, NOESY, HMBC, CD	[2]
50.	Hyperascyrin L	C34H44O4	516.3240	aerial parts	UV, IR, HRESIMS, 1H NMR, 13C NMR, HSQC, HMBC, NOESY, CD	[5]
51.	Hyperascyrin M	C34H44O5	532.3189	aerial parts	UV, IR, HRESIMS, 1H NMR, 13C NMR, HSQC, HMBC, NOESY, CD	[5]
52.	Hyperascyrin N	C34H44O6	548.3138	aerial parts	UV, IR, HRESIMS, 1H NMR, 13C NMR, HSQC, HMBC, NOESY, CD	[5]
53.	Hypermongone A	C32H48O5	512.3502	aerial parts	HRESIMS, 1H NMR, 13C NMR	[5]
54.	Hypermongone B	C32H48O5	512.3502	aerial parts	HRESIMS, 1H NMR, 13C NMR	[5]
				whole plant	MS, 1H NMR, 13C NMR	[3]
55.	Hypermongone C	C31H46O5	498.3345	aerial parts	HRESIMS, 1H NMR, 13C NMR	[5]
56.	Hypermongone D	C31H46O5	498.3345	aerial parts	HRESIMS, 1H NMR, 13C NMR	[5]
57.	Norascyronone A	C26H34O2	378.2559	aerial parts	${\left[\alpha \right]}_D^{25}$, mp, UV, IR, ESIMS, HRESIMS, 1H NMR, 13C NMR, DEPT, 1H-1H COSY, HSQC, NOESY, HMBC, CD	[43]
58.	Norascyronone B	C26H34O3	394.2508	aerial parts	${\left[\alpha \right]}_D^{22}$, UV, IR, ESIMS, HRESIMS, 1H NMR, 13C NMR, DEPT, 1H-1H COSY, HSQC, NOESY, HMBC, CD	[43]
59.	Norascyronone C	C26H36O2	380.2715	aerial parts	${\left[\alpha \right]}_D^{22}$, UV, IR, ESIMS, HRESIMS, 1H NMR, 13C NMR, DEPT, 1H-1H COSY, HSQC, NOESY, HMBC, CD	[43]
60.	Ascyronone A	C31H46O5	498.3345	whole plant	UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, DEPT, HMBC, ROESY	[3]
61.	Ascyronone B	C32H48O5	512.3502	whole plant	UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, DEPT, HMBC, ROESY	[3]
62.	Ascyronone C	C33H46O4	506.3396	whole plant	UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, DEPT, HMBC, ROESY	[3]
63.	Ascyronone D	C32H48O5	512.3502	whole plant	UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, DEPT, HMBC, ROESY	[3]
64.	Hyperibone J	C31H46O5	498.3345	whole plant	MS, 1H NMR, 13C NMR	[3]
65.	Hyperscabrone G	C32H48O5	512.3502	whole plant	MS, 1H NMR, 13C NMR	[3]
66.	Ascyronone E	C38H50O4	570.3709	flowers	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, NOESY, HMBC, CD	[6]
67.	Ascyronone F	C38H50O5	586.3658	flowers	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, NOESY, HMBC, CD	[6]
68.	Ascyronone G	C33H42O5	518.3032	flowers	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, NOESY, HMBC, CD	[6]
69.	Hypelodin B	C38H48O4	568.3553	flowers	MS, 1H NMR, 13C NMR	[6]
70.	Hypercohin K	C33H40O4	500.2927	flowers	MS, 1H NMR, 13C NMR	[6]
71.	Hyperforin	C35H52O4	536.3866	aerial parts	HPLC	[44]
72.	Furohyperforin	C35H52O5	552.3815	flowers	MS, 1H NMR, 13C NMR	[6]
				whole plant	EI-MS, 1H NMR, 13C NMR	[24]
73.	Furoadhyperforin	C36H54O5	566.3971	whole plant	EI-MS, 1H NMR, 13C NMR	[24]
74.	Hypercohin G	C35H52O4	536.3866	flowers	MS, 1H NMR, 13C NMR	[6]
75.	Hyphenrone X	C35H44O4	528.3240	flowers	MS, 1H NMR, 13C NMR	[6]
76.	Ascyronine A	C38H52O7	620.3713	aerial parts	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, HMQC, HMBC, ROESY, CD	[10]
77.	Ascyronine B	C35H52O7	584.3713	aerial parts	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, HMQC, HMBC, ROESY, CD	[10]
78.	Ascyronine C	C35H54O8	602.3819	aerial parts	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, HMQC, HMBC, ROESY, CD	[10]
79.	Hunascynol A	C33H42O6	534.2981	aerial parts	${\left[\alpha \right]}_D$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, DEPT, HMBC, ROESY, CD	[9]
80.	Hunascynol B	C33H42O6	534.2981	aerial parts	${\left[\alpha \right]}_D$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, DEPT, HMBC, ROESY, CD	[9]
81.	Hunascynol C	C33H40O5	516.2876	aerial parts	${\left[\alpha \right]}_D$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, DEPT, HMBC, ROESY, CD	[9]
82.	Hunascynol D	C31H46O6	514.3294	aerial parts	${\left[\alpha \right]}_D$, mp, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, DEPT, HMBC, ROESY, CD	[9]
83.	Hunascynol E	C31H46O6	514.3294	aerial parts	${\left[\alpha \right]}_D$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, DEPT, HMBC, ROESY, CD	[9]
84.	Hunascynol F	C31H46O6	514.3294	aerial parts	${\left[\alpha \right]}_D$, mp, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, DEPT, HMBC, ROESY, CD	[9]
85.	Hunascynol G	C31H46O5	498.3345	aerial parts	${\left[\alpha \right]}_D$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, DEPT, HMBC, ROESY, CD	[9]
86.	Hunascynol H	C30H44O5	484.3189	aerial parts	${\left[\alpha \right]}_D$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, DEPT, HMBC, ROESY, CD	[9]
87.	Hunascynol I	C31H46O6	514.3294	aerial parts	${\left[\alpha \right]}_D$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, DEPT, HMBC, ROESY, CD	[9]
88.	Hunascynol J	C31H46O6	514.3294	aerial parts	${\left[\alpha \right]}_D$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, DEPT, HMBC, ROESY, CD	[9]
89.	Hyperbeanol A	C33H42O6	534.2981	aerial parts	ESI-MS, 1H NMR, 13C NMR	[9]
90.	Hyperbeanol B	C33H42O6	534.2981	aerial parts	ESI-MS, 1H NMR, 13C NMR	[9]
91.	Hyperbeanol C	C33H42O6	534.2981	aerial parts	ESI-MS, 1H NMR, 13C NMR	[9]
92.	Hyperbeanol D	C33H42O7	550.2931	aerial parts	ESI-MS, 1H NMR, 13C NMR	[9]
93.	Hypercohone G	C33H40O5	516.2876	aerial parts	ESI-MS, 1H NMR, 13C NMR	[9]
94.	Hyperascone A	C30H42O7	514.2931	aerial parts	${\left[\alpha \right]}_D$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, DEPT, NOESY, HMBC, CD	[11]
95.	Hyperascone B	C31H44O7	528.3087	aerial parts	${\left[\alpha \right]}_D$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, DEPT, HMQC, NOESY, HMBC, CD	[11]

UV: Ultraviolet spectrophotometry; IR: Infrared spectroscopy; mp: Melting point; CD: Circular dichroism; MS: Mass spectrometry; EI-MS: Electron impact mass spectrometry; ESI-MS: Electrospray ionization mass spectrometry; HRESIMS: High-resolution electrospray ionization mass spectrometry; ¹H-NMR: Hydrogen-1 nuclear magnetic resonance spectrometry; ¹³C-NMR: Carbon-13 nuclear magnetic resonance spectrometry; 1D NMR: One-dimensional nuclear magnetic resonance spectrometry; 2D NMR: Two-dimensional nuclear magnetic resonance spectrometry; HMBC: ¹H Detected heteronuclear multiple bond correlation; HMQC: ¹H Detected heteronuclear multiple quantum coherence; HSQC: Heteronuclear singular quantum correlation; COSY: Correlation spectroscopy; ROESY: Rotating frame Overhauser effect spectroscopy; NOESY: Nuclear Overhauser effect spectroscopy; DEPT: Distortionless enhancement by polarization transfer.

, Figure 3), each with unique structural characteristics and pharmacological properties, making them a compelling subject for ongoing research.

6.2. Xanthones and Dibenzo-1,4-dioxane Derivatives

Xanthones (dibenzo-γ-pyrones) are a vital class of oxygenated heterocycles commonly found as secondary metabolites in Hypericum species [45]. The structural configuration and substituents present in the tricyclic scaffold of xanthones play a crucial role in dictating their diverse biological activities. Due to their distinctive structural framework and medicinal relevance, xanthones have garnered significant attention as potential drug candidates [46]. Presently, H. ascyron has yielded eight dibenzo-1,4-dioxane derivatives (96–103) and thirty-one additional xanthones (104–134) (

Table 2. Xanthones and dibenzo-1,4-dioxane derivatives isolated or identified from Hypericum ascyron L.

No.	Name	Formula	Exact Theoretical Molecular Weight	Source	Characterization Method	Ref.
96.	Hyperdioxane A	C30H34O8	522.2254	roots	${\left[\alpha \right]}_D^{23}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, HSQC, HMBC, NOESY, CD	[47]
97.	Hyperdioxane B	C15H14O6	290.0790	roots	${\left[\alpha \right]}_D^{24}$, mp, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, HSQC, HMBC, NOESY, CD	[47]
98.	Hyperdioxane C	C15H16O7	308.0896	roots	UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, HSQC, HMBC, NOESY, ROESY, CD	[32]
99.	Hyperdioxane D	C14H14O6	278.0790	roots	UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, HSQC, HMBC, NOESY, ROESY, CD	[32]
100.	Hyperdioxane E	C15H16O7	308.0896	roots	UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, HSQC, HMBC, NOESY, ROESY, CD	[32]
101.	Hyperdioxane F	C15H16O7	308.0896	roots	UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, HSQC, HMBC, NOESY, ROESY, CD	[32]
102.	Sampsone B	C16H18O7	322.1053	roots	${\left[\alpha \right]}_D$, UV, IR, 1H NMR, 13C NMR, 1H-1H COSY, HSQC, HMBC, NOESY, CD	[32]
103.	3,7,10a-Trimethoxy-1,4,4a,10a-tetrahydrodibenzo-p-dioxin-1-one	C15H16O6	292.0947	roots	${\left[\alpha \right]}_D^{22}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, HSQC, HMBC, NOESY, ROESY, CD	[32]
104.	1,6-Dihydroxy-5,7-dimethoxyxanthone	C15H12O6	288.0634	aerial parts	EI-MS, 1H NMR, 13C NMR	[13]
105.	Euxanthone	C13H8O4	228.0423	aerial parts	1H NMR, 13C NMR	[13]
				aerial parts	EI-MS, 1H NMR, 13C NMR	[12]
106.	6-O-palmitolyl-1,6-dihydroxy-5,7-dimethoxyxanthone	C31H42O7	526.2931	aerial parts	UV, EI-MS, 1H NMR, 13C NMR	[13]
107.	2-Methoxyxanthone	C14H10O3	226.0630	aerial parts	EI-MS, 1H NMR, 13C NMR	[12]
108.	1-Hydroxy-7-methoxyxanthone	C14H10O4	242.0579	aerial parts	EI-MS, 1H NMR, 13C NMR	[12]
				whole plant	mp, EI-MS, 1H NMR, 13C NMR	[42]
109.	5-Chloro-1,6-dihydroxy-3-methoxy-8-methylxanthone	C15H11ClO5	306.0295	aerial parts	UV, IR, HRESIMS, 1H NMR, 13C NMR, DEPT, HMBC, NOESY	[12]
110.	3,6-Dihydroxy-1,7-dimethoxyxanthone	C15H12O6	288.0634	aerial parts	UV, IR, HRESIMS, 1H NMR, 13C NMR, DEPT, HMQC, HMBC, NOESY	[12]
				aerial parts	UV, 1H NMR, 13C NMR	[11]
111.	7-Methoxy-1,5,6-trihydroxyxanthone	C14H10O6	274.0477	aerial parts	EI-MS, 1H NMR, 13C NMR	[12]
112.	Toxyloxanthone B	C18H14O6	326.0790	aerial parts	EI-MS, 1H NMR, 13C NMR	[12]
				whole plant	mp, EI-MS, 1H NMR, 13C NMR	[42]
113.	1,3,6,7-Tetrahydroxy-8-(3-methylbut-2-enyl)xanthone	C18H16O6	328.0947	aerial parts	EI-MS, 1H NMR, 13C NMR	[12]
				whole plant	MS, 1H NMR, 13C NMR	[48]
114.	1,3,5-Trihydroxy-6,7-[2′-(1-methylethenyl)-dihydrofurano]-xanthone	C18H14O6	326.0790	aerial parts	IR, HRESIMS, 1H NMR, 13C NMR, HMBC	[14]
115.	1,3,5-Trihydroxy-6,7-[2′-(1-hydroxy-1-methylethyl)-dihydrofurano]-xanthone	C18H16O7	344.0896	aerial parts	IR, HRESIMS, 1H NMR, 13C NMR, HMBC	[14]
116.	1,3,5-Trihydroxy-6-O-prenyl-xanthone	C18H16O6	328.0947	aerial parts	IR, HRESIMS, 1H NMR, 13C NMR, HMBC	[14]
117.	1,3,5-Trihydroxy-3′,3′-dimethyl-2H-pyran[6,7]xanthen-9-one	C18H14O6	326.0790	aerial parts	MS, 1H NMR, 13C NMR	[14]
118.	1,3-Dihydroxy-5-methoxyxanthone	C14H10O5	258.0528	aerial parts	MS, 1H NMR, 13C NMR	[14]
119.	1,3,5,6-Tetrahydroxyxanthone	C13H8O6	260.0321	aerial parts	MS, 1H NMR, 13C NMR	[14]
				aerial parts	UV, 1H NMR, 13C NMR	[11]
120.	1,7-Dihydroxyxanthone	C13H8O4	228.0423	aerial parts	ESI-MS, 1H NMR	[19]
				aerial parts	UV, 1H NMR, 13C NMR	[11]
				whole plant	mp, EI-MS, 1H NMR, 13C NMR	[42]
121.	2,3-Dimethoxyxanthone	C15H12O4	256.0736	whole plant	mp, EI-MS, 1H NMR, 13C NMR	[42]
122.	1,3,6,7-Tetrahydroxyxanthone	C13H8O6	260.0321	aerial parts	ESI-MS, 1H NMR	[19]
				aerial parts	UV, 1H NMR, 13C NMR	[11]
123.	6-Deoxyisojacareubin	C18H14O5	310.0841	whole plant	1H NMR, 13C NMR	[22]
124.	Paxanthone	C19H16O6	340.0947	whole plant	1H NMR, 13C NMR	[22]
125.	1,3,5-Trihydroxy-6-O-(3-methylbut-2-enyl)-xanthone	C18H16O6	328.0947	aerial parts	UV, HRESIMS, 1H NMR, 13C NMR	[11]
126.	3,7-Dihydroxy-1,6-dimethoxy-xanthone	C15H12O6	288.0634	aerial parts	UV, HRESIMS, 1H NMR, 13C NMR, HMBC	[11]
127.	Subalatin	C24H20O9	452.1107	aerial parts	UV, 1H NMR, 13C NMR	[11]
128.	Sampsone C	C18H16O8	360.0845	aerial parts	UV, 1H NMR, 13C NMR	[11]
129.	Deprenylated rheediaxanthone	C18H16O6	328.0947	aerial parts	UV, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, HMQC, HMBC	[11]
130.	1,3,7-Trihydroxy-xanthone	C13H8O5	244.0372	aerial parts	UV, 1H NMR, 13C NMR	[11]
131.	1,5-Dihydroxy-8-methoxy-xanthone	C14H10O5	258.0528	aerial parts	UV, 1H NMR, 13C NMR	[11]
132.	1,4,8-Trihydroxy-xanthone	C13H8O5	244.0372	aerial parts	UV, 1H NMR, 13C NMR	[11]
133.	3,4-Dihydroxy-2-methoxy-xanthone	C14H10O5	258.0528	aerial parts	UV, 1H NMR, 13C NMR	[11]
134.	2-Hydroxy-xanthone	C13H8O3	212.0473	aerial parts	UV, 1H NMR, 13C NMR	[11]

UV: Ultraviolet spectrophotometry; IR: Infrared spectroscopy; mp: Melting point; CD: Circular dichroism; MS: Mass spectrometry; EI-MS: Electron impact mass spectrometry; ESI-MS: Electrospray ionization mass spectrometry; HRESIMS: High-resolution electrospray ionization mass spectrometry; ¹H-NMR: Hydrogen-1 nuclear magnetic resonance spectrometry; ¹³C-NMR: Carbon-13 nuclear magnetic resonance spectrometry; HMBC: ¹H Detected heteronuclear multiple bond correlation; HMQC: ¹H Detected heteronuclear multiple quantum coherence; HSQC: Heteronuclear singular quantum correlation; COSY: Correlation spectroscopy; ROESY: Rotating frame Overhauser effect spectroscopy; NOESY: Nuclear Overhauser effect spectroscopy; DEPT: Distortionless enhancement by polarization transfer.

, Figure 4), each offering unique possibilities for further exploration and pharmacological investigation.

6.3. Flavonoids

Flavonoids constitute a group of natural polyphenolic compounds that are abundant in Hypericum species [45]. These plant secondary metabolites play pivotal roles in various biological processes and responses to environmental stimuli within plants. In addition to being common constituents of human diets, flavonoids exhibit antioxidant, antimicrobial, and anti-inflammatory properties, thereby contributing to disease prevention and overall health. The bioactivity of flavonoids is intricately linked to the structural arrangement of substituents in their characteristic C₆-C₃-C₆ rings [49]. Currently, twenty-three flavonoids (135–157) have been isolated and characterized from H. ascyron (

Table 3. Flavonoids isolated or identified from Hypericum ascyron L.

No.	Name	Formula	Exact Theoretical Molecular Weight	Source	Characterization Method	Ref.
135.	Kaempferol	C15H10O6	286.0477	aerial parts	mp, UV	[50]
				aerial parts	1H NMR, EI-MS	[13]
				aerial parts	mp, ESI-MS, 1H NMR, 13C NMR	[21]
				aerial parts	MS, 1H NMR, 13C NMR	[14]
				aerial parts	1H NMR, 13C NMR	[51]
				aerial parts	ESI-MS, 1H NMR, 13C NMR	[19]
				aerial parts	ESI-MS, 1H NMR, 13C NMR	[18]
				aerial parts	UV, 1H NMR, 13C NMR	[11]
				whole plant	mp, 1H NMR, 13C NMR	[29]
				whole plant	Chemical reactions, mp, UV, IR, 13C NMR	[20]
				whole plant	Chemical reactions, mp, UV, IR	[52]
				whole plant	ESI-MS, 1H NMR, 13C NMR	[53]
				whole plant	HPLC	[35]
				whole plant	mp, EI-MS, 1H NMR, 13C NMR	[42]
				whole plant	UPLC-Q-TOF-MS	[17]
136.	Quercetin	C15H10O7	302.0427	aerial parts	mp, UV	[50]
				aerial parts	HPLC	[44]
				aerial parts	1H NMR, EI-MS	[13]
				aerial parts	MS, 1H NMR, 13C NMR	[14]
				aerial parts	mp, ESI-MS, 1H NMR, 13C NMR	[21]
				aerial parts	1H NMR, 13C NMR	[51]
				aerial parts	ESI-MS, 1H NMR, 13C NMR	[19]
				aerial parts	MS, 1H NMR, 13C NMR, DEPT	[15]
				aerial parts	ESI-MS, 1H NMR, 13C NMR	[18]
				aerial parts	UV, 1H NMR, 13C NMR	[11]
				whole plant	Chemical reactions, mp, UV, IR, 13C NMR	[20]
				whole plant	mp, ESI-MS, 1H NMR, 13C NMR	[53]
				whole plant	HPLC	[35]
				whole plant	UPLC-Q-TOF-MS	[17]
				whole plant	Chemical reactions, mp, IR	[54]
				whole plant	Chemical reactions, elemental analysis, mp, UV, IR, 1H NMR	[52]
				whole plant	mp, EI-MS, 1H NMR, 13C NMR	[42]
137.	Luteolin	C15H10O6	286.0477	aerial parts	ESI-MS, 1H NMR, 13C NMR	[18]
				aerial parts	UV, 1H NMR, 13C NMR	[11]
138.	Catechin	C15H14O6	290.0790	whole plant	UPLC-Q-TOF-MS	[17]
139.	Isoquercitrin	C21H20O12	464.0955	whole plant	Chemical reactions, elemental analysis, mp, UV, IR	[52]
				whole plant	Chemical reactions, mp, UV, IR, 1H NMR, 13C NMR	[20]
				whole plant	HPLC	[35]
140.	Trifolin	C21H20O11	448.1006	aerial parts	${\left[\alpha \right]}_D^{20}$, mp, UV, acid and enzymatic hydrolysis	[50]
141.	Hyperoside	C21H20O12	464.0955	aerial parts	${\left[\alpha \right]}_D^{20}$, mp, UV, acid and enzymatic hydrolysis	[50]
				aerial parts	HPLC	[44]
				aerial parts	mp, ESI-MS, 1H NMR, 13C NMR	[21]
				aerial parts	1H NMR, 13C NMR	[51]
				aerial parts	ESI-MS, 1H NMR, 13C NMR	[19]
				aerial parts	UV, 1H NMR, 13C NMR	[11]
				whole plant	Chemical reactions, mp, UV, IR, MS, 1H NMR	[54]
				whole plant	Chemical reactions, elemental analysis, mp, UV, IR, 1H NMR	[52]
				whole plant	mp, 1H NMR, 13C NMR	[53]
				whole plant	mp, 1H NMR, 13C NMR	[29]
				whole plant	HPLC	[35]
				whole plant	mp, EI-MS, 1H NMR, 13C NMR	[42]
				whole plant	UPLC-Q-TOF-MS	[17]
142.	3,5,8,3′,4′-Pentahydroxyflavone	C15H10O7	302.0427	whole plant	ESI-MS, 1H NMR, 13C NMR	[53]
				whole plant	mp, 1H NMR, 13C NMR	[29]
143.	6-Methyl-5-hydroxy-7,4′-dimethoxyflavanone	C18H18O5	314.1154	whole plant	1H NMR, 13C NMR	[22]
144.	Kaempferol-3-O-β-D-galactoside	C21H20O11	448.1006	aerial parts	ESI-MS, 1H NMR, 13C NMR	[19]
				whole plant	UPLC-Q-TOF-MS	[17]
145.	Kaempferol 3-O-β-D-glucoside	C21H20O11	448.1006	aerial parts	1H NMR, 13C NMR	[51]
				aerial parts	ESI-MS, 1H NMR, 13C NMR	[19]
				aerial parts	UV, 1H NMR, 13C NMR	[11]
				whole plant	1H NMR, 13C NMR	[53]
				whole plant	mp, 1H NMR, 13C NMR	[29]
				whole plant	HPLC	[35]
				whole plant	UPLC-Q-TOF-MS	[17]
146.	Quercitrin	C21H20O11	448.1006	whole plant	mp, EI-MS, 1H NMR, 13C NMR	[42]
147.	Quercetin 3-O-α-L-arabinofuranoside	C20H18O11	434.0849	aerial parts	mp, ESI-MS, 1H NMR, 13C NMR	[21]
				aerial parts	UV, 1H NMR, 13C NMR	[11]
148.	Quercetin-3-O-β-D-glucoside	C21H20O12	464.0955	aerial parts	1H NMR, 13C NMR	[51]
				aerial parts	ESI-MS, 1H NMR, 13C NMR	[19]
				aerial parts	UV, 1H NMR, 13C NMR	[11]
				whole plant	mp, 1H NMR, 13C NMR	[53]
				whole plant	mp, 1H NMR, 13C NMR	[29]
				whole plant	UPLC-Q-TOF-MS	[17]
149.	Kaempferol 3-O-β-(2′′-acetyl) galactopyranoside	C23H22O12	490.1111	aerial parts	MS, 1H NMR, 13C NMR, DEPT	[15]
150.	kaempferol-3-O-(6′′-O-crotonoyl)-β-D-glucopyranoside	C25H24O12	516.1268	aerial parts	ESI-MS, 1H NMR, 13C NMR	[19]
151.	Isoquercetin	C21H20O12	464.0955	aerial parts	UV, ESI-MS, 1H NMR, 13C NMR	[16]
152.	Isohyperoside	C21H20O12	464.0955	aerial parts	UV, ESI-MS, 1H NMR, 13C NMR	[16]
153.	3,8”-Biapigenin	C30H18O10	538.0900	aerial parts	ESI-MS, 1H NMR, 13C NMR	[18]
				aerial parts	UV, 1H NMR, 13C NMR	[11]
154.	Hinokiflavone	C30H18O10	538.0900	aerial parts	UV, 1H NMR	[11]
155.	Kaempferol (6–8′′) apigenin	C30H18O11	554.0849	aerial parts	ESI-MS, 1H NMR, 13C NMR	[18]
156.	5’,3′′′-Dihydroxyrobustaflavone	C30H18O12	570.0798	aerial parts	ESI-MS, 1H NMR, 13C NMR	[18]
157.	Rutin	C27H30O16	610.1534	whole plant	Chemical reactions, elemental analysis, mp, UV, IR	[52]
				aerial parts	HPLC	[44]
				whole plant	HPLC	[35]
				whole plant	mp, EI-MS, 1H NMR, 13C NMR	[42]

UV: Ultraviolet spectrophotometry; IR: Infrared spectroscopy; mp: Melting point; HPLC: High-performance liquid chromatography; MS: Mass spectrometry; EI-MS: Electron impact mass spectrometry; ESI-MS: Electrospray ionization mass spectrometry; UPLC-Q-TOF-MS: Ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry; ¹H-NMR: Hydrogen-1 nuclear magnetic resonance spectrometry; ¹³C-NMR: Carbon-13 nuclear magnetic resonance spectrometry; DEPT: Distortionless enhancement by polarization transfer.

, Figure 5), offering a wealth of possibilities for exploring their therapeutic potential and bioactive properties further.

6.4. Phenolics

Over the past few years, phenolics have attracted considerable notice because of their connection to the possible prevention of chronic and degenerative illnesses, the primary reasons for death and incapacitation in industrialized nations. The intake of phenolics through diet has been linked to beneficial health outcomes [55]. A total of twenty-one phenolics (158–178) have been successfully isolated and characterized from both the aerial parts and the whole plant of H. ascyron (

Table 4. Phenolics isolated or identified from Hypericum ascyron L.

No.	Name	Formula	Exact Theoretical Molecular Weight	Source	Characterization Method	Ref.
158.	p-Hydroxybenzoic acid	C7H6O3	138.0317	aerial parts	1H NMR, 13C NMR	[51]
				aerial parts	ESI-MS, 1H NMR	[19]
				aerial parts	UV, 1H NMR, 13C NMR	[11]
159.	4-Hydroxybenzoic acid methyl ester	C8H8O3	152.0473	aerial parts	EI-MS, 1H NMR, 13C NMR	[13]
160.	Protocatechuic acid	C7H6O4	154.0266	aerial parts	1H NMR, 13C NMR	[51]
				aerial parts	ESI-MS, 1H NMR	[19]
				aerial parts	ESI-MS, 1H NMR, 13C NMR	[18]
				aerial parts	UV, 1H NMR, 13C NMR	[11]
161.	Protocatechuic acid methyl ester	C8H8O4	168.0423	aerial parts	ESI-MS, 1H NMR, 13C NMR	[18]
162.	Vanillic acid	C8H8O4	168.0423	aerial parts	UV, 1H NMR, 13C NMR	[11]
163.	p-Coumaric acid	C9H8O3	164.0473	aerial parts	ESI-MS, 1H NMR	[19]
				aerial parts	UV, 1H NMR, 13C NMR	[11]
164.	Gallic acid	C7H6O5	170.0215	aerial parts	TLC, 1H NMR	[19]
165.	Ethyl gallate	C9H10O5	198.0528	aerial parts	UV, 1H NMR, 13C NMR	[11]
166.	3-O-Caffeoylquinic acid methyl ester	C17H20O9	368.1107	aerial parts	MS, 1H NMR, 13C NMR	[14]
				aerial parts	UV, 1H NMR, 13C NMR	[11]
167.	Methyl caffeate	C10H10O4	194.0579	aerial parts	MS, 1H NMR, 13C NMR	[14]
168.	5,7-Dihydroxy-2-isopropylchromone	C12H12O4	220.0736	aerial parts	MS, 1H NMR, 13C NMR	[14]
				aerial parts	UV, 1H NMR	[11]
169.	Hyperfaberol F	C13H14O4	234.0892	aerial parts	UV, 1H NMR, 13C NMR	[11]
170.	2,2’,5,6’-Tetrahydroxybenzophenone	C13H10O5	246.0528	whole plant	1H NMR, 13C NMR, DEPT	[22]
171.	2,4-Dihydroxy-6-(4-hydroxybenzoyloxyl-)-benzoyl acid	C14H10O7	290.0427	aerial parts	ESI-MS, 1H NMR, 13C NMR	[18]
172.	2,4-Dihydroxy-6-(3,4-dihydroxybenzoyloxyl-)-benzoyl acid	C14H10O8	306.0376	aerial parts	ESI-MS, 1H NMR, 13C NMR	[18]
173.	2-(3,4-Dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone	C15H10O8	318.0376	aerial parts	ESI-MS, 1H NMR, 13C NMR	[18]
174.	Chlorogenic acid	C16H18O9	354.0951	whole plant	UPLC-Q-TOF-MS	[17]
				whole plant	UV	[54]
175.	4-O-Caffeoylquinic acid	C16H18O9	354.0951	whole plant	UPLC-Q-TOF-MS	[17]
176.	5-O-Caffeoylquinic acid	C16H18O9	354.0951	whole plant	UPLC-Q-TOF-MS	[17]
177.	9,9’-O-Di-(E)-feruloyl-(-)-secoisolariciresinol	C40H42O12	714.2676	aerial parts	ESI-MS, 1H NMR, 13C NMR	[19]
178.	Cinchonain Ia	C24H20O9	452.1107	aerial parts	UV, 1H NMR, 13C NMR	[11]

UV: Ultraviolet spectrophotometry; TLC: Thin-layer chromatography; HPLC: High-performance liquid chromatography; MS: Mass spectrometry; EI-MS: Electron impact mass spectrometry; ESI-MS: Electrospray ionization mass spectrometry; UPLC-Q-TOF-MS: Ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry; ¹H-NMR: Hydrogen-1 nuclear magnetic resonance spectrometry; ¹³C-NMR: Carbon-13 nuclear magnetic resonance spectrometry; DEPT: Distortionless enhancement by polarization transfer.

, Figure 6), underscoring the plant’s richness in these bioactive compounds.

6.5. Steroids and Triterpenoids

Steroids and triterpenoids, known for their diverse biological activities, have emerged as crucial components in plants. Their abundance and medicinal significance have attracted considerable scientific interest [56,57]. A total of twenty-eight steroids and triterpenoids (179–206) have been isolated and identified from various parts of H. ascyron, including its aerial parts and whole plant (

Table 5. Steroids and triterpenoids isolated or identified from Hypericum ascyron L.

No.	Name	Formula	Exact Theoretical Molecular Weight	Source	Characterization Method	Ref.
179.	Friedelin	C30H50O	426.3862	aerial parts	EI-MS, 1H NMR, 13C NMR	[12]
				aerial parts	${\left[\alpha \right]}_D$, 1H NMR, 13C NMR	[58]
				aerial parts	1H NMR, 13C NMR	[59]
				whole plant	EI-MS, 1H NMR, 13C NMR	[24]
180.	Glutinol	C30H50O	426.3862	whole plant	1H NMR, 13C NMR, DEPT	[22]
181.	Betulinic acid	C30H48O3	456.3603	aerial parts	1H NMR, 13C NMR	[13]
				aerial parts	UV, 1H NMR, 13C NMR	[11]
				whole plant	ESI-MS, 1H NMR, 13C NMR	[53]
				whole plant	mp, 1H NMR, 13C NMR	[29]
				whole plant	1H NMR, 13C NMR, DEPT	[22]
182.	3,4-seco-Olean-13(18)-ene-12,19-dione-3-oic acid	C30H46O4	470.3396	aerial parts	${\left[\alpha \right]}_D^{20}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, DEPT, 1H-1H COSY, HMBC, X-ray	[59]
				aerial parts	${\left[\alpha \right]}_D$, UV, IR, HRESIMS, 1H NMR, 13C NMR, DEPT, 1H-1H COSY, HMBC, CD, X-ray	[58]
183.	Betulinic acid methyl ester	C31H50O3	470.3760	aerial parts	UV, 1H NMR, 13C NMR	[11]
184.	Ursolic acid	C30H48O3	456.3603	whole plant	ESI-MS, 1H NMR, 13C NMR	[53]
				whole plant	mp, 1H NMR, 13C NMR	[29]
185.	19α-Hydroxyursolic acid	C30H48O4	472.3553	aerial parts	mp, ESI-MS, 1H NMR, 13C NMR	[21]
186.	6β,19α-Dihydroxy ursolic acid	C30H48O5	488.3502	aerial parts	mp, ESI-MS, 1H NMR, 13C NMR	[21]
187.	Myriaboric acid	C30H46O6	502.3294	aerial parts	mp, ESI-MS, 1H NMR, 13C NMR	[21]
188.	Ergosterol peroxide	C28H44O3	428.3290	aerial parts	1H NMR, 13C NMR	[59]
189.	β-Sitosterol	C29H50O	414.3862	aerial parts	1H NMR	[13]
				aerial parts	TLC	[19]
				aerial parts	TLC, ESI-MS, 1H NMR	[21]
				aerial parts	1H NMR, 13C NMR	[51]
				whole plant	GC-MS	[20]
				whole plant	Chemical reaction, mp, TLC	[42]
				whole plant	1H NMR, 13C NMR, DEPT	[22]
190.	Campesterol	C28H48O	400.3705	whole plant	GC-MS	[20]
				aerial parts	1H NMR, 13C NMR	[51]
191.	Stigmasterol	C29H48O	412.3705	aerial parts	TLC, ESI-MS, 1H NMR	[21]
				aerial parts	1H NMR, 13C NMR	[51]
				whole plant	GC-MS	[20]
				whole plant	1H NMR, 13C NMR	[22]
192.	β-Sitosterol-β-D-glucoside	C35H60O6	576.4390	whole plant	IR, 1H NMR, 13C NMR	[20]
				whole plant	ESI-MS, 1H NMR, 13C NMR	[53]
				whole plant	mp, 1H NMR, 13C NMR	[29]
				whole plant	Chemical reaction, mp, TLC	[42]
193.	β-Sitosterol-β-D-glucoside palmitoyl ester	C51H90O7	814.6687	whole plant	IR, 1H NMR, 13C NMR	[20]
194.	β-Sitosterol-β-D-glucoside stearoyl ester	C53H94O7	842.7000	whole plant	IR, 1H NMR, 13C NMR	[20]
195.	β-Sitosterol-β-D-glucoside oleoyl ester	C53H92O7	840.6843	whole plant	IR, 1H NMR, 13C NMR	[20]
196.	β-Sitosterol-β-D-glucoside linoleoyl ester	C53H90O7	838.6687	whole plant	IR, 1H NMR, 13C NMR	[20]
197.	Campesterol-β-D-glucoside	C34H58O6	562.4233	whole plant	IR, 1H NMR, 13C NMR	[20]
198.	Campesterol-β-D-glucoside palmitoyl ester	C50H88O7	800.6530	whole plant	IR, 1H NMR, 13C NMR	[20]
199.	Campesterol-β-D-glucoside stearoyl ester	C52H92O7	828.6843	whole plant	IR, 1H NMR, 13C NMR	[20]
200.	Campesterol-β-D-glucoside oleoyl ester	C52H90O7	826.6687	whole plant	IR, 1H NMR, 13C NMR	[20]
201.	Campesterol-β-D-glucoside linoleoyl ester	C52H88O7	824.6530	whole plant	IR, 1H NMR, 13C NMR	[20]
202.	Stigmasterol-β-D-glucoside	C35H58O6	574.4233	whole plant	IR, 1H NMR, 13C NMR	[20]
203.	Stigmasterol-β-D-glucoside palmitoyl ester	C51H88O7	812.6530	whole plant	IR, 1H NMR, 13C NMR	[20]
204.	Stigmasterol-β-D-glucoside stearoyl ester	C53H92O7	840.6843	whole plant	IR, 1H NMR, 13C NMR	[20]
205.	Stigmasterol-β-D-glucoside oleoyl ester	C53H90O7	838.6687	whole plant	IR, 1H NMR, 13C NMR	[20]
206.	Stigmasterol-β-D-glucoside linoleoyl ester	C53H88O7	836.6530	whole plant	IR, 1H NMR, 13C NMR	[20]

UV: Ultraviolet spectrophotometry; IR: Infrared spectroscopy; mp: Melting point; TLC: Thin-layer chromatography; CD: Circular dichroism; GC-MS: Gas chromatography–mass spectrometry; EI-MS: Electron impact mass spectrometry; ESI-MS: Electrospray ionization mass spectrometry; HRESIMS: High-resolution electrospray ionization mass spectrometry; ¹H-NMR: Hydrogen-1 nuclear magnetic resonance spectrometry; ¹³C-NMR: Carbon-13 nuclear magnetic resonance spectrometry; HMBC: ¹H Detected heteronuclear multiple bond correlation; COSY: Correlation spectroscopy; DEPT: Distortionless enhancement by polarization transfer.

, Figure 7).

6.6. Volatile Components

The significance of volatile components has surged in popularity over the past decade, particularly due to their integration into traditional medicinal practices as holistic modalities. These complex substances comprise hundreds of individual components with diverse properties such as antimicrobial, antiviral, antibiotic, anti-inflammatory, and antioxidant activities [60]. A total of fifty-nine volatile components (207–265) have been isolated and identified in H. ascyron, originating from both its aerial parts and whole plant (

Table 6. Volatile components isolated from Hypericum ascyron L.

No.	Name	Formula	Exact Theoretical Molecular Weight	Source	Characterization Method	Ref.
207.	Acetone	C3H6O	58.0419	whole plant	GC-MS	[23]
208.	Hexanal	C6H12O	100.0888	whole plant	GC-MS	[23]
209.	Nonane	C9H20	128.1565	whole plant	GC-MS	[23]
210.	2-Heptanone, 6-methyl-	C8H16O	128.1201	whole plant	GC-MS	[23]
211.	5-Hepten-2-one, 6-methyl-	C8H14O	126.1045	whole plant	GC-MS	[23]
212.	Furan, 2-pentyl-	C9H14O	138.1045	whole plant	GC-MS	[23]
213.	Cyclohexanone,2-(1-methylethyl)-	C9H16O	140.1201	whole plant	GC-MS	[23]
214.	4-Nonanone	C9H18O	142.1358	whole plant	GC-MS	[23]
215.	Undecane	C11H24	156.1878	whole plant	GC-MS	[23]
216.	Nonanal	C9H18O	142.1358	whole plant	GC-MS	[23]
217.	Decanal	C10H20O	156.1514	whole plant	GC-MS	[23]
218.	2-Undecanone	C11H22O	170.1671	whole plant	GC-MS	[23]
219.	Tricyclo[5.4.0.0(2,8)]undec-9-ene,2,6,6,9-tetramethyl-	C15H24	204.1878	whole plant	GC-MS	[23]
220.	Azulene,1,2,3,4,5,6,7,8-octahydro-1,4-dimethyl-7-(1-methylethenyl)-,[1s-(1α,4α,7α)]-	C15H24	204.1878	whole plant	GC-MS	[23]
221.	1,2,4-Metheno-1H-indene, octahydro-1,7a-dimethyl-5-(1-methylethyl)-	C15H24	204.1878	whole plant	GC-MS	[23]
222.	Copaene	C15H24	204.1878	whole plant	GC-MS	[23]
223.	Cyclobuta[1,2-a:3,4-a′]dicyclopentene, decahydro-3a-methyl-6-methylene-1-(1-methylethyl)-, (1S,3aS,3bR,6aS,6bR)-	C15H24	204.1878	whole plant	GC-MS	[23]
224.	β-Cubebene	C15H24	204.1878	whole plant	GC-MS	[23]
225.	6,10-Dimethyl-5,9-undecadien-2-one	C13H22O	194.1671	whole plant	GC-MS	[23]
226.	1,6,10-Dodecatriene,7,11-dimethyl-3-methylene-,(E)-	C15H24	204.1878	whole plant	GC-MS	[23]
227.	γ-Muurolene	C15H24	204.1878	whole plant	GC-MS	[23]
228.	α-muurolene	C15H24	204.1878	whole plant	GC-MS	[23]
229.	β-Cadinene	C15H24	204.1878	whole plant	GC-MS	[23]
230.	Calamenene	C15H22	202.1722	whole plant	GC-MS	[23]
231.	α-calacorene	C15H20	200.1565	whole plant	GC-MS	[23]
232.	Aromadendrene oxide 2	C15H24O	220.1827	whole plant	GC-MS	[23]
233.	(-)-Spathulenol	C15H24O	220.1827	whole plant	GC-MS	[23]
234.	3,4,4-Trimethyl-3-(3-oxo-but-1-enyl)-bicyclo[4.1.0]heptan-2-one	C14H20O2	220.1463	whole plant	GC-MS	[23]
235.	1H-Cycloprop[e]azulen-4-ol, decahydro-1,1,4,7-tetramethyl-	C15H26O	222.1984	whole plant	GC-MS	[23]
236.	α-Cadinol	C15H26O	222.1984	whole plant	GC-MS	[23]
237.	Azulene,1,4-dimethyl-7-(1-methylethyl)-	C15H18	198.1409	whole plant	GC-MS	[23]
238.	6-Isopropenyl-4,8a-dimethyl-,1,2,3,5,6,7,8,8a-octahydro-naphthalen-2-ol	C15H24O	220.1827	whole plant	GC-MS	[23]
239.	(+)-Nootkatone	C15H22O	218.1671	whole plant	GC-MS	[23]
240.	spiro[4.5]decan-7-one,1,8-dimethyl-8,9-epoxy-4-isopropyl-	C15H24O2	236.1776	whole plant	GC-MS	[23]
241.	2-(4a,8-Dimethyl-6-oxo-1,2,3,4,4a,5,6,8a-octahydro-naphthalen-2-yl)-propionaldehyde	C15H22O2	234.1620	whole plant	GC-MS	[23]
242.	2-Pentadecanone, 6,10,14-trimethyl-	C18H36O	268.2766	whole plant	GC-MS	[23]
243.	1,2-Benzenedicarboxylic acid, bis(2-methylpropyl) ester	C16H22O4	278.1518	whole plant	GC-MS	[23]
244.	3,7,11,15-Tetramethyl-2-hexadecen-1-ol	C20H40O	296.3079	whole plant	GC-MS	[23]
245.	Nonadecane	C19H40	268.3130	whole plant	GC-MS	[23]
246.	5,9,13-Pentadecatrien-2-one, 6,10,14-trimethyl-,(E,E)-	C18H30O	262.2297	whole plant	GC-MS	[23]
247.	Hexadecanoic acid, methyl ester	C17H34O2	270.2559	whole plant	GC-MS	[23]
248.	Dibutyl phthalate	C16H22O4	278.1518	whole plant	GC-MS	[23]
249.	n-Hexadecanoic acid	C16H32O2	256.2402	whole plant	GC-MS	[23]
250.	Hexadecanoic acid, ethyl ester	C18H36O2	284.2715	whole plant	GC-MS	[23]
251.	Eicosane	C20H42	282.3287	whole plant	GC-MS	[23]
252.	Heneicosane	C21H44	296.3443	whole plant	GC-MS	[23]
253.	Octadecane	C18H38	254.2974	whole plant	EI-MS, 1H NMR	[24]
254.	Octacosane	C28H58	394.4539	whole plant	EI-MS, 1H NMR	[24]
255.	n-Hexacosanol	C26H54O	382.4175	aerial parts	GC-MS	[13]
256.	n-Octacosanol	C28H58O	410.4488	aerial parts	GC-MS	[13]
				whole plant	1H NMR, 13C NMR	[24]
257.	n-Nonacosanol	C29H60O	424.4644	aerial parts	mp, EI-MS, 1H NMR	[21]
258.	n-Triacontanol	C30H62O	438.4801	aerial parts	GC-MS	[13]
259.	Hendecanoic acid	C11H22O2	186.1620	whole plant	1H NMR, 13C NMR	[24]
260.	Octadecanoic acid	C18H36O2	284.2715	whole plant	EI-MS, 1H NMR, 13C NMR	[24]
261.	Arachidic acid	C20H40O2	312.3028	whole plant	EI-MS, 1H NMR	[24]
262.	Lignoceric acid	C24H48O2	368.3654	aerial parts	GC-MS	[13]
263.	Hexacosanoic acid	C26H52O2	396.3967	aerial parts	GC-MS	[13]
				whole plant	EI-MS, 1H NMR	[24]
264.	Octacosanoic acid	C28H56O2	424.4280	aerial parts	GC-MS	[13]
265.	Triacontanoic acid	C30H60O2	452.4593	aerial parts	GC-MS	[13]
				whole plant	EI-MS, 1H NMR	[24]

mp: Melting point; GC-MS: Gas chromatography–mass spectrometry; EI-MS: Electron impact mass spectrometry; ¹H-NMR: Hydrogen-1 nuclear magnetic resonance spectrometry; ¹³C-NMR: Carbon-13 nuclear magnetic resonance spectrometry.

, Figure 8).

6.7. Other Components

Aside from the compound types previously mentioned, an additional five unique compound types (266–270) have been effectively isolated and identified from different sections of H. ascyron, encompassing its roots, aerial parts, and the entire plant (

Table 7. Other components isolated or identified from Hypericum ascyron L.

No.	Name	Formula	Exact Theoretical Molecular Weight	Source	Characterization Method	Ref.
266.	Eremophil-9,11(13)-dien-8β,12-olide	C15H20O2	232.1463	roots	${\left[\alpha \right]}_D^{27}$, UV, IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, HSQC, HMBC, NOESY, CD	[47]
267.	Carascynol A	C21H34O4	350.2457	aerial parts	IR, HRESIMS, 1H NMR, 13C NMR, 1H-1H COSY, DEPT, HMBC, ROESY, X-ray	[61]
268.	Esculetin	C9H6O4	178.0266	aerial parts	ESI-MS, 1H NMR, 13C NMR	[18]
269.	7-Isopentenyloxy-8-methoxycoumarin	C15H16O4	260.1049	aerial parts	UV, 1H NMR, 13C NMR	[11]
270.	Bridelionoside C	C20H36O9	420.2359	whole plant	1H NMR, 13C NMR	[22]

UV: Ultraviolet spectrophotometry; IR: Infrared spectroscopy; CD: Circular dichroism; HRESIMS: High-resolution electrospray ionization mass spectrometry; ¹H-NMR: Hydrogen-1 nuclear magnetic resonance spectrometry; ¹³C-NMR: Carbon-13 nuclear magnetic resonance spectrometry; HMBC: ¹H Detected heteronuclear multiple bond correlation; HSQC: Heteronuclear singular quantum correlation; COSY: Correlation spectroscopy; ROESY: Rotating frame Overhauser effect spectroscopy; NOESY: Nuclear Overhauser effect spectroscopy; DEPT: Distortionless enhancement by polarization transfer.

, Figure 9). These findings underscore the remarkable diversity and complexity of bioactive compounds present in H. ascyron, highlighting its potential for further exploration and utilization in pharmacological and medical research.

7. Pharmacology

While H. ascyron has long been recognized for its medicinal properties, contemporary pharmacological investigations have unveiled a diverse array of effects associated with this plant. These effects span antioxidant, antidiabetic, anti-inflammatory, analgesic, antidepressant, cytotoxic, antimicrobial, and hepatoprotective activities, among others.

7.1. Antioxidant Activity

The methanol extract from H. ascyron has a total phenolic content of 56.7 mg chlorogenic acid/g and a total flavonoid content of 14.6 mg quercetin/g. This extract exhibits strong radical scavenging activities, with IC₅₀ values of 21.1 μg/mL for DPPH and 12.6 μg/mL for ABTS assays. In comparison, the methanol extract from young sprouts of H. ascyron contains 197.1 mg ferulic acid/kg and demonstrates robust DPPH scavenging activities with an IC₅₀ of 16.9 μg/mL [28]. Furthermore, the methanol extract of H. ascyron displays a good DPPH radical scavenging ability with an IC₅₀ of 34.32 μg/mL, while the petroleum ether extract and ethyl acetate extract show no DPPH scavenging ability. In the ABTS assay, the methanol extract of H. ascyron exhibits the highest ABTS scavenging ability with an IC₅₀ of 24.55 μg/mL, followed by the ethyl acetate extract with an IC₅₀ of 30.36 μg/mL, whereas the petroleum ether extract shows no scavenging ability. Results from the FRAP experiment align closely with those from the ABTS assay. Further exploration of compounds isolated from H. ascyron reveals that quercetin (136), hyperoside (141), quercetin-3-O-β-D-glucoside (148), kaempferol (135), and rutin (157) exhibit potent DPPH scavenging abilities, surpassing those of BHT [53].

H. ascyron flavonoids demonstrate superior DPPH scavenging ability, exhibiting an IC₅₀ of 2.71 μg/mL, which is similar to that of the positive control, vitamin C, with an IC₅₀ of 1.73 μg/mL. Additionally, the flavonoids exhibit a higher capacity to scavenge hydroxyl radicals than vitamin C, with an IC₅₀ of 0.08 mg/mL compared to 0.12 mg/mL for vitamin C. The flavonoids also effectively inhibit the degradation of β-carotene and display good reducing ability, close to vitamin C, as observed in the FRAP experiment. While the total antioxidant capacity of flavonoids at the same concentration is not as high as that of vitamin C, they still demonstrate a noteworthy level of antioxidant capacity. The flavonoids can substantially inhibit DNA strand oxidation and ring opening, with their inhibitory ability strengthening with increasing concentration, thereby effectively combating oxidative damage [62].

Reports suggest that hyperoside (141) plays a protective role in heart health. Authors evaluated the protective abilities of isoquercitrin (151) and isohyperoside (152) from H. ascyron against hydrogen peroxide-induced damage in H9C2 cardiomyocytes. Studies indicate that 151 and 152 exhibit similar protective effects to 141, with 152 particularly effective in reducing lactate dehydrogenase leakage, malondialdehyde levels, and increasing superoxide dismutase activity. This study represents the first documentation of the myocardial protective effects of 151 and 152, potentially achieved by shielding the cell membrane from oxidative damage [16].

7.2. Antidiabetic Activity

The methanol extract from H. ascyron (IC₅₀ = 151.47 μg/mL) and the ethyl acetate extract (IC₅₀ = 755.8 μg/mL) exhibit significant α-glucosidase inhibitory effects, with their inhibition rates being notably higher than that of the positive control, acarbose (IC₅₀ = 1081.27 μg/mL). Quercetin (136) (IC₅₀ = 8.86 μg/mL), kaempferol (135) (IC₅₀ = 73.69 μg/mL), and ursolic acid (184) (IC₅₀ = 3.38 μg/mL), isolated from these extracts, demonstrate potent α-glucosidase inhibitory activity. Following research on yeast-derived α-glucosidase inhibition, further investigations were conducted on rat small intestine α-glucosidase inhibition. The ethyl acetate extract (IC₅₀ = 703.78 μg/mL), methanol extract (IC₅₀ = 1142.68 μg/mL), 136 (IC₅₀ = 131.78 μg/mL), and 135 (IC₅₀ = 70.96 μg/mL) also display considerable inhibitory activity against rat small intestine α-glucosidase. The in vivo assessment of the antidiabetic potency of these extracts, conducted on diabetic mice induced by alloxan, showed a noteworthy reduction in serum blood glucose concentrations following the intragastric delivery of ethyl acetate extract (500 mg/kg) and methanol extract (500 mg/kg) over a period of 8 d, along with lowered blood lipid levels of total cholesterol and triglyceride. Moreover, oxidative stress and tissue damage were mitigated through reduced malondialdehyde levels and increased superoxide dismutase levels. These findings suggest that H. ascyron may serve as a valuable source of natural antioxidants and α-glucosidase inhibitors for managing hyperglycemia and its complications [53]. Flavonoids from H. ascyron (IC₅₀ = 0.237 mg/mL) also exhibit potent α-glucosidase inhibitory activity [62].

7.3. Anti-Inflammatory and Analgesic Effects

The inhibitory rates of the methanol extract from H. ascyron (at concentrations of 2.5, 12.5, 25, 50 μg/mL) against secretory group II phospholipase A2, cyclooxygenase-2, 5-lipoxygenase, and lyso-PAF acetyltransferase are 77.8%, 41.8%, 83.9%, and 37.7%, respectively [63]. At 80 μg/mL, the methanol extract of H. ascyron inhibits nitric oxide (NO) production (24.8%) and IL-6 production (37.6%) [17], indicating its potential in treating inflammatory diseases. H. ascyron extracts demonstrate hyaluronidase inhibitory activity and dose-dependent inhibition of iNOS-derived NO, COX-2-derived PGE2, and pro-inflammatory cytokines like TNF-α, IL-6, and IL-1β in LPS-induced 264.7 cells, with observed cell toxicity at higher concentrations. These results suggest significant anti-inflammatory effects of H. ascyron extracts and their potential as therapeutic agents [64].

Longistylione C (8) (IC₅₀ = 3.9 μM) exhibits evident anti-inflammatory activity in LPS-induced RAW264.7 cells [8]. Hyperdioxane B (97) effectively suppresses IL-1β production in LPS-activated microglial cells, achieving a 72.3% inhibition rate at a concentration of 6.3 μM without causing cytotoxicity [32]. Additionally, in a study examining human neutrophil elastase (HNE), which is implicated in inflammatory processes, the floral extract of H. ascyron exhibits a considerable impact on HNE activity. The isolated metabolites exhibited inhibitory activity against HNE. Specifically, furohyperforin (72), ascyronone E (66), and ascyronone G (68) demonstrated HNE inhibitory activity with respective IC₅₀ values of 2.4, 4.3, and 4.5 μM [6].

The rise in industrialization has resulted in increased particulate matter in the atmosphere, leading to heightened occurrences of asthma and respiratory issues. Researchers have investigated the therapeutic impact of H. ascyron methanol extract on airway inflammation. Their findings revealed that the methanol extract reduced NO secretion and mRNA expression of pro-inflammatory cytokines in MH-S cells. In animal studies, the methanol extract decreased neutrophil infiltration and enhanced T cells in the airways of mice, thereby reducing inflammatory markers such as CXCL-1, IL-17, MIP-2, and TNF-α. Moreover, the methanol extract effectively lowered the mRNA expression of MIP-2 and TNF-α in the lungs of mice. This suggests that H. ascyron methanol extract is efficacious in preventing airway inflammation triggered by coal fly ash in cells and diesel exhaust particles in mice [27].

The median lethal dose of the ethyl acetate fraction and n-butanol fraction from H. ascyron is 22.13 g/kg and 31.37 g/kg, respectively. The minimum lethal dose of the water fraction and petroleum ether fraction from H. ascyron is 58.66 g/kg and 60.12 g/kg, respectively. Compared to the control group, rats treated with the ethyl acetate fraction exhibited significantly reduced foot and joint swelling indices, along with significantly increased thymus and spleen indices. This suggests that the ethyl acetate fraction from H. ascyron is effective in treating adjuvant arthritis in rats [65].

The xylene-induced mouse ear swelling and carrageenan-induced rat foot swelling models are acute non-specific inflammation models. The study results indicate that H. ascyron extract has a substantial inhibitory effect on acute non-specific inflammation in a dose-dependent manner, suggesting its promising anti-inflammatory effects on acute and early inflammation. Experimental data on the impact of H. ascyron extract on capillary permeability demonstrate its ability to reduce capillary permeability and exudation in cases of acute and early inflammation. Additionally, in an immune inflammatory model using the egg white-induced rat foot swelling model, H. ascyron extract also displayed significant inhibitory effects. Using the hot plate method, a classic fast pain experimental model, the findings suggest that H. ascyron extract possesses analgesic properties against fast pain induced by the hot plate method in mice. Furthermore, in a twisting experiment model representing chronic persistent inflammatory pain, the results indicate that H. ascyron extract elevates the pain threshold induced by acetic acid in mice, illustrating its analgesic effects on chronic persistent pain. In conclusion, H. ascyron extract showcases notable anti-inflammatory and analgesic effects [26].

7.4. Antidepressant Activity

The study investigated the antidepressant effects of different doses of H. ascyron decoction (5 g/kg, 10 g/kg, and 15 g/kg) administered orally to mice. The medium and high-dose groups significantly reduced tail suspension immobility time and forced swimming immobility time in mice, with no significant difference compared to the fluoxetine group, indicating an antidepressant effect of H. ascyron. Subsequent acute toxicity experiments revealed 40 g/kg as the maximum tolerable dose for mice, equivalent to 120 times the daily adult dosage, suggesting the clinical safety of H. ascyron [23]. Ascyronines A–C (76–78) were assessed for their antidepressant activity by inhibiting serotonin and noradrenaline reuptake in rat brain synaptosomes. Ascyronines B–C (77–78) showed weak antidepressant effects in the serotonin mode [10].

The neural differentiation effect of longistyliones A–D (6–9) was investigated by introducing the compound (at a concentration of 10 μM) into the culture medium on the second day of the differentiation process. Longistylione C (8) exhibited superior neurogenesis compared to other compounds, particularly in facilitating serotonergic neuronal differentiation in vitro. Administering 8 (2 mg/kg) reduced depression-like behaviors in mice, comparable to fluoxetine in immobility time tests. Treatment with 8 during neuronal differentiation led to increased serotonergic neuron production in embryonic stem cells, resulting in elevated 5-hydroxytryptamine levels and improved behavior under stress. The potential mechanism of H. ascyron’s antidepressant effects could involve phloroglucinol compounds stimulating neural regeneration in vivo [34].

7.5. Cytotoxicity

The methanol extract from H. ascyron young sprouts at 200 μg/mL exhibited modest anticancer activity against Calu-6 and SNU-601 tumor cell lines, inhibiting growth by 44% and 46%, respectively [28]. Crude, petroleum ether, ethyl acetate, and aqueous extracts of H. ascyron showed no inhibitory effects on human lung cancer cell proliferation for A549 and NCI-H292 cell lines [11]. Authors evaluated the anticancer potential of H. ascyron extract, the study discovered that the combination of kaempferol 3-O-β-(2′′-acetyl) galactopyranoside (149) and quercetin (136) notably boosted antiproliferative activity when compared to the individual compounds or the extract’s active fraction alone. The synergistic effect of these compounds suggests promise for H. ascyron in cancer treatment by inducing apoptosis in HeLa cells, indicating a novel aspect of its anticancer activity. This study supports the clinical use of H. ascyron and proposes its potential for innovative anticancer drug development [66].

Ascyrone A (1) and hyperascyrin N (10) showed moderate cytotoxic effects on Hep3B cells, with compound 10 also demonstrating minor inhibitory activity against SNU-387 cells [8]. The cytotoxic potential of hyperascyrones A–H (42–49) was evaluated against five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480) as well as the immortalized non-cancerous human lung epithelial cell line BEAS-2B in vitro, with cisplatin as the positive control. Among these compounds, hyperascyrone C (44), hyperascyrone G (48), and hyperascyrone H (49) displayed moderate cytotoxic effects on the tested cancer cell lines. More specifically, compounds 44 and 48 demonstrated notable cytotoxicity towards HL-60 cells, boasting IC₅₀ values of 4.22 and 8.36 μM, respectively [2]. Additionally, norascyronones A–C (57–59) underwent assessment for their cytotoxic potential against three distinct human cancer cell lines, namely SK-BR-3, PANC-1, and ECA-109.

Norascyronone A (57) exhibited moderate cytotoxic activity against SK-BR-3 and PANC-1 cell lines, with respective IC₅₀ values of 4.3 and 8.4 μM. Additionally, Norascyronone B (58) demonstrated activity towards SK-BR-3 and ECA-109 cell lines, with IC₅₀ values of 7.8 and 12.7 μM, respectively. Furthermore, tomoeones A–H (21–23, 25–28, 30) underwent testing for their cytotoxic effects on human cancer cell lines, including multidrug-resistant (MDR) cancer cell lines such as KB-C2 and K562/Adr. Among these compounds, tomoeone F (27) stood out for its impressive cytotoxicity against KB cells, boasting an IC₅₀ value of 6.2 μM. Moreover, compound 27 also exhibited cytotoxic effects on MDR cancer cell lines KB-C2 and K562/Adr, outperforming doxorubicin in terms of potency [1].

Carascynol A (267) was assessed for its activity against three human colon cancer cell lines: HCT116, SW480, and LoVo. Compound 267 showed the strongest activity towards LoVo cells, achieving an IC₅₀ value of 12.30 μM, while its cytotoxicity was less pronounced against SW480 and HCT116 cell lines (with IC₅₀ values of 18.33 and 24.57 μM, respectively). Significantly, 267 had minimal impact on the viability of peripheral blood mononuclear cells, highlighting its selective toxicity towards colon cancer cells [61]. Bioassays indicated that both hunascynol A (79) and hunascynol B (80) strongly suppressed the growth of colon cancer HCT116 cells (with IC₅₀ values of 6.87 and 9.86 μM, respectively), triggered G1 cell cycle arrest, and modified the expression of target proteins. Compounds 79 and 80 feature a 1,2-seco-acylphloroglucinol core that forms a lactone ring, which may be a contributing factor to their anti-colon-cancer activity. Furthermore, hunascynol C (81) and hunascynol E (83) demonstrated a dose-dependent reduction in sub-intestinal vessels in zebrafish embryos, and potential target genes were identified using real-time PCR [9].

7.6. Antimicrobial Activity

The antibacterial properties of a 60% ethanol extract derived from H. ascyron were evaluated against several bacterial strains, including Enterobacter cloacae, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, and Micrococcus luteus (M. luteus). The findings revealed that the most susceptible bacteria to the extract were Escherichia coli, Staphylococcus aureus, and particularly M. luteus. Notably, the minimum bactericidal concentration of the H. ascyron extract against M. luteus was determined to be the same as the minimum inhibitory concentration (MIC), which was measured at 20 mg/mL. Furthermore, it was observed that the extract from H. ascyron had the ability to trigger cell death in M. luteus via the apoptosis pathway [31].

The authors identified kaempferol 3-O-β-(2′′-acetyl) galactopyranoside (149) and quercetin (136) as antibacterial compounds present in H. ascyron. These compounds induced bacterial cell death with apoptotic features at moderate concentrations by disrupting cell membranes, potentially leading to irreversible membrane-mediated apoptosis. This study lays the foundation for the clinical use of H. ascyron and highlights its potential in the development of novel antibacterial drugs, especially targeting antibiotic-resistant bacteria [15].

Multiple compounds, specifically hypascyrin A (11), hypascyrin C (13), hypascyrin E (15), and ent-hyphenrone J (16), have exhibited antimicrobial activity towards methicillin-resistant Staphylococcus aureus (MRSA), with MIC₅₀ values of 4.0, 8.0, 2.0, and 4.0 μM, respectively. These compounds also showed activity against Bacillus subtilis, with MIC values matching those observed for MRSA, at 4.0, 4.0, 2.0, and 4.0 μM, respectively [7]. Additionally, the methanol extract from H. ascyron underwent partitioning with chloroform, ethyl acetate, and n-butanol after being suspended in water.

The chloroform fraction exhibited strong antibacterial activity against MRSA. Furthermore, 1,3,6,7-tetrahydroxy-8-(3-methylbut-2-enyl)xanthone (113) isolated from the chloroform fraction displayed significant inhibitory effects against MRSA [48]. Moreover, the hexane fraction of the H. ascyron extract (128 mg/mL) showcased antibacterial activity against a strain of MRSA possessing the NorA multidrug-efflux transporter, the primary characterized MDR pump in this species [67]. Hyperdioxane A (96) exhibited anti-HIV activity with an IC₅₀ of 5.3 μM and a therapeutic index value of 7.2 against HIV NL4-3 in the MT-4 cells. Among hyperascyrones A–H (42–49), only hyperascyrone F (47) demonstrated moderate activity in preventing the cytopathic effects of HIV-1 in MT-4 cells, with concentration for 50% of maximal effect (EC₅₀) value of 2.43 μM and a selectivity index of 5.63 [2].

7.7. Hepatoprotective Effect

The ethyl acetate fraction (250 mg/kg) and n-butanol fraction (250 mg/kg) of H. ascyron have shown the ability to alleviate acute liver injury in mice caused by carbon tetrachloride. Additionally, the ethyl acetate fraction (250 mg/kg) of H. ascyron has demonstrated efficacy in alleviating alcohol-induced acute liver injury in mice [68]. Hyperascyrin H (38) and hyperascyrin I (39) demonstrated protective effects against HepG2 cell damage induced by paracetamol at a concentration of 10 μM [4]. Likewise, at the same concentration of 10 μM, hyperascyrin L (50) and hyperascyrin N (52) also showed hepatoprotective properties against paracetamol-induced damage in HepG2 cells [5]. Research has revealed that kaempferol (135) (EC₅₀ = 84.3 μM) and quercetin (136) (EC₅₀ = 239.3 μM) isolated from H. ascyron possess the highest hepatoprotective effects against tacrine-induced cytotoxicity in HepG2 cells [51].

7.8. Other Pharmacological Effects

The treatment outcomes of 100 cases of asthmatic chronic bronchitis indicated that H. ascyron possesses a distinct therapeutic effect, yielding a total effectiveness rate of 85%. Notably, expectorant and the disappearance of wheezing sounds exhibit superior efficacy compared to asthma relief and cough suppression. H. ascyron is associated with fewer side effects, with only a minimal number of individuals experiencing dry throat and stomach discomfort following medication. These reactions typically subside upon discontinuation of the medication [69]. Pharmacological studies have demonstrated that quercetin (136) and hyperoside (141) are the primary active ingredients responsible for alleviating asthma, relieving cough, and expelling phlegm [70].

The ethanol extract from H. ascyron exhibited higher antioxidant activity and better inhibitory effects against α-glucosidase, xanthine oxidase, tyrosinase, collagenase, and elastase compared to the aqueous extract, along with pore-tightening activity. Overall, H. ascyron extracts possess antioxidant, carbohydrate degradation inhibitory, antigout, whitening, antiwrinkle, and pore-tightening activities, making them a valuable functional resource [71]. Furthermore, H. ascyron flavonoids were found to significantly reduce tyrosinase activity (IC₅₀ = 46.99 μg/mL), with a competitive inhibition type mechanism that inhibits melanin production [62].

Individual compounds from H. ascyron also showed various levels of neuroprotective effects. Ascyrone A (1) exhibited mild neuroprotective activity against corticosterone-induced damage in PC12 cells at 10 μM [8]. Hyperascyrin A (31) and hyperascyrin H (38) demonstrated mild neuroprotection against glutamate-induced toxicity in SK-N-SH cells at 10 μM [4], while hyperascyrins L-N (50–52) exhibited strong neuroprotection against the same toxicity at the same concentration [5]. The 60% ethanol extract of H. ascyron (100 μg/mL) displayed strong histamine-release inhibitory activity from mast cells (inhibition rate of 90.0%) and had no effect on NO production by macrophages. Additionally, a study on the in vitro elimination of cerebral cysticercosis using ethanol extract showed promising results, with 0.5 g of ethanol extract equivalent to 50 mg of praziquantel (a positive drug) [72].

8. Discussion

We have presented a thorough overview of the traditional uses, geographical distribution, botanical description, phytochemistry, and pharmacology of H. ascyron, a traditional medicinal plant. H. ascyron contains a diverse array of phytochemicals, with a total of two hundred and seventy reported compounds, including phloroglucinols, xanthones, flavonoids, phenolics, steroids, triterpenoids, volatile components, and other compounds. The pharmacological effects of these compounds and H. ascyron extracts have been elucidated, revealing antioxidant, antidiabetic, anti-inflammatory, analgesic, antidepressant, cytotoxic, antimicrobial, and hepatoprotective activities. Additionally, it has shown efficacy in treating bronchitis, neuroprotection, and inhibiting key enzymes in clinical diseases. Phloroglucinols, xanthones, and flavonoids are particularly highlighted as the primary constituents responsible for these pharmacological effects.

The whole plant of H. ascyron has long been lauded for its medicinal properties and is prominently featured in classic books on Chinese herbal medicines. As a result, significant academic research has been focused on deciphering the chemical makeup of H. ascyron. Among the compounds present in H. ascyron, phloroglucinols hold particular importance due to their uniqueness as a chemical class exclusive to the Hypericum genus. Ninety-five compounds belonging to this class have been discovered in H. ascyron, exhibiting chemical structural variations with side chains bearing various functional groups such as acyl, hydroxyl, prenyl, and geranyl. Exploring the biological activities of these unique phloroglucinols offers a compelling path for deeper investigation, which may uncover therapeutically useful, safe, and potent compounds.

Moreover, comprehensive research has revealed a wide array of pharmacological effects associated with H. ascyron, with a primary emphasis on its antioxidant, anti-inflammatory, and analgesic capabilities. Nevertheless, it should be emphasized that certain studies have relied exclusively on H. ascyron extracts instead of isolated pure compounds. Furthermore, the exploration of H. ascyron’s pharmacological effects lacks comprehensive coverage, with many underlying mechanisms remaining unclear. Therefore, there is a pressing need for further exploration of the pharmacological activities of H. ascyron.

In summary, there are several important research paths to pursue in relation to H. ascyron. Firstly, a comprehensive study delving into the plant’s chemical components is needed to ascertain the precise elements that contribute to its pharmacological actions. Secondly, despite promising pharmacological effects and cytotoxicity demonstrated by certain elements in cellular trials, further affirmation through animal model experiments is essential. Following this, an in-depth examination of its pharmacological processes is due to offer theoretical direction and technical assistance for pharmaceutical advancement and clinical utilization. Lastly, it is vital to methodically verify and refine the conventional usages of H. ascyron, thereby releasing its entire capability and extending its useful applications.

9. Conclusions

Despite the wealth of findings, there remains a lack of a detailed review regarding the traditional uses, geographical distribution, botanical description, phytochemistry, and pharmacology of H. ascyron. Therefore, the central aim of this review is to undertake a comprehensive analysis of existing research on H. ascyron, drawing from multiple databases to address these specific facets. Moreover, this review aims to pinpoint potential avenues for future investigations, such as the isolation and identification of novel compounds present in H. ascyron, extensive pharmacological assessments, and the delineation of its underlying mechanisms of action. The findings of this inquiry are expected to lay a robust foundation for the separation and identification of components, development of products, and clinical utilization of H. ascyron.