Research Progress on Chemical Constituents and Pharmacological Activities of Menispermi Rhizoma

Abstract

Menispermi Rhizoma, the rhizome of Menispermum dauricum DC., is a traditional Chinese medicine, which has the effect of clearing away heat and detoxification, dispelling wind, and relieving pain. It is often used in the treatment of sore throat, enteritis, dysentery, and rheumatism. The chemical constituents of M. Rhizoma mainly include alkaloids, phenolic acids, quinones, cardiotonic glycosides, and so on. Modern pharmacological studies have proved that M. Rhizoma has the effects of anti-tumour, anti-inflammation, anti-oxidation, bacteriostasis, cardio-cerebrovascular protection, anti-depression and anti-Alzheimer’s disease. In recent years, the chemical constituents of M. Rhizoma have been found continuously, and the pharmacological studies have deepened gradually. This paper reviews the research progress on the chemical composition and pharmacological effects of M. Rhizoma, to provide a basis for further research and development of its medicinal value.

1. Introduction

Menispermi Rhizoma is the dried rhizome of Menispermum dauricum DC. It is mainly produced in Northeast China, North China, East China, and Shaanxi. It has the effect of clearing heat and detoxifying, dispelling wind, and relieving pain, and is mainly used for sore throat, pyretic diarrhoea, dysentery, and rheumatic paralysis [1]. Modern research has shown that the various chemical components contained in M. Rhizoma, including alkaloids, phenolic acids, quinones, cardiac glycosides, and polysaccharides, have a variety of pharmacological activities, such as anti-tumour, anti-inflammatory, antioxidant, antibacterial, cardiovascular, antidepressant, and anti-Alzheimer’s disease [2,3]. This review reports the research progress on chemical constituents and pharmacological activities of M. Rhizoma up to 2023. First, all the chemical components of M. Rhizoma that have been discovered so far are listed. The most abundant component of M. Rhizoma, the alkaloid, was systematically classified based on their structural characteristics. After that, the pharmacological activities and applications of M. Rhizoma are also reported according to the type of clinical disease treated. In summary, this review will provide a theoretical basis for further research and the utilization of M. Rhizoma in the future.

2. Chemical Composition

So far, more than 100 compounds, including alkaloids, phenolic acids, quinones, cardiac glycosides, polysaccharides, and other chemical components, have been isolated and identified from M. Rhizoma [3,4].

2.1. Alkaloids

Alkaloids, as the signature components of M. Rhizoma, are also the most abundant class of components, with a content of 1.7–2.5% [3,4]. The diversity of alkaloid structures in M. Rhizoma is mainly distinguished by their parent nucleus structure, the type and number of substituents, and chiral carbon atoms. The main species include bisbenzylisoquinolines (

Table 1. Alkaloids of M. Rhizoma.

No.	Alkaloids	Formula	Mass	Reference
1	dauricine	C38H44N2O6	624.3	[5]
2	daurinoline	C37H42N2O6	610.3	[6]
3	dauricinoline	C37H42N2O6	610.3	[6]
4	daurisoline	C37H42N2O6	610.3	[6]
5	dauricicline	C36H40N2O6	596.3	[7]
6	dauricoline	C36H40N2O6	596.3	[7]
7	(R,R)-N-Desmethlydauricine	C37H42N2O6	610.3	[8]
8	O-methyldauricine	C39H46N2O6	638.3	[7]
9	tetrandrine	C38H42N2O6	622.3	[6]
10	thalifortine	C37H40N2O6	608.3	[7]
11	costaricine	C35H38N2O6	582.3	[9]
12	cycleapeltine	C37H40N2O6	608.3	[10]
13	homoaromoline	C37H40N2O6	608.3	[10]
14	(+)-1,3,4-dehydrocepharanthine	C36H32N2O6	588.2	[11]
15	(+)-1,3,4-dehydrocepharanthine-2′β-N-oxide	C36H32N2O7	604.2	[11]
16	(1R, 1′R)-dauricine-2β-N-oxide	C37H42N2O7	626.3	[12]
17	(1R, 1′R)-daurisoline-2β-N-oxide	C38H44N2O7	640.3	[12]
18	(1R, 1′R)-dauricine-2α-N-oxide	C38H44N2O7	640.3	[12]
19	(1R, 1ʹR)-dauricisoline A-2α-N-oxide	C38H45N2O7+	641.3	[12]
20	(1R, 1′R)-daurisoline-2′α-N-oxide	C37H42N2O7	626.3	[12]
21	(1R, 1′R)-dauricine-2′α-N-oxide	C38H44N2O7	640.3	[12]
22	(1R, 1′R)-dauricisoline C-2′α-N-oxide	C39H47N2O7+	655.3	[12]
23	(1R, 1′R)-dauricine-2′β-N-oxide	C38H44N2O7	640.3	[12]
24	(1R, 1′R)-dauricisoline E-2′β-N-oxide	C39H47N2O7+	655.3	[12]
25	(1R, 1′R)-dauricisoline A	C38H45N2O6+	625.3	[12]
26	(1R, 1′R)-dauricisoline B	C37H43N2O6+	611.3	[12]
27	(1R, 1′R)-dauricisoline C	C38H45N2O6+	625.3	[12]
28	(1R, 1′R)-dauricisoline D	C37H43N2O6+	611.3	[12]
29	(1R, 1′R)-dauricisoline E	C39H47N2O6+	639.3	[12]
30	(1R, 1′R)-espinin	C36H40N2O6	596.3	[12]
31	(1′R)-dauricisoline F	C38H43N2O6+	623.3	[13]
32	(1R, 1′R)-dauricisoline G	C44H48N2O7	716.3	[13]
33	(1R, 1′R)-dauricisoline H	C37H43N2O6+	611.3	[13]
34	(1R, 1′R)-dauricisoline I	C36H40N2O6	596.3	[13]
35	(1R, 1′R)-dauricisoline J	C38H46N2O62+	626.3	[13]
36	(1′R)-pavermenidaurine	C38H41N2O7+	637.3	[13]
37	cissampentin	C37H40N2O6	608.3	[9]
38	cycleatjehenine	C37H36N2O6	604.3	[9]
39	neosutchuenenine	C36H40N2O6	596.3	[10]
40	cissampentine A	C36H38N2O6	594.3	[11]
41	cissampentine B	C37H40N2O6	608.3	[11]
42	(−)-pseudocurine	C36H38N2O6	594.3	[11]
43	sutchueneneonine	C36H40N2O6	596.3	[10]
44	sutchuenenine	C36H40N2O6	596.3	[10]
45	secoisotetrandrine	C38H40N2O8	652.3	[10]
46	tuduranine	C18H19NO3	297.1	[7]
47	iso-corydine	C20H23NO4	341.2	[7]
48	cepharanthine	C19H19NO3	309.1	[7]
49	menisperine	C21H26NO4+	356.2	[14]
50	magnoflorine	C20H24NO4+	342.2	[14]
51	N-formyldehydroanonain	C18H13NO3	291.1	[15]
52	N-demethyl-N-formyldehydronuciferine	C19H17NO3	307.1	[15]
53	sinotumine G	C18H15NO3	293.1	[16]
54	6-acetyl-5,6-dihydro-1,2-dimethoxy-4H-dibenzo[de,g]-quinoline	C20H19NO3	321.1	[17]
55	N-formylmornuciferin	C19H19NO3	309.1	[15]
56	N-formylannonaine	C18H15NO3	293.1	[15]
57	N-acetylasimilobine	C19H19NO3	309.1	[16]
58	stepharine	C18H19NO3	297.1	[18]
59	telisatin A	C20H15NO4	333.1	[16]
60	telazoline	C17H12N2O2	276.1	[11]
61	oxidized nantenine	C19H13NO5	335.1	[7]
62	atherospermidine	C18H11NO4	305.1	[16]
63	dauriporphine	C20H17NO5	351.1	[14]
64	menisporphine	C19H15NO4	321.1	[14]
65	6-O-demethylmenisporphine	C18H13NO4	307.1	[14]
66	dauriporphinoline	C19H15NO5	337.1	[14]
67	bianfugecine	C18H13NO3	291.1	[19]
68	bianfugedine	C18H11NO4	305.1	[19]
69	oxoisoaporphine A	C18H11NO4	305.1	[20]
70	oxoisoaporphine B	C18H13NO4	307.1	[20]
71	menisoxoisoaporphine B	C19H15NO3	305.1	[17]
72	menispeimin A	C17H11NO3	277.1	[16]
73	sinotumine D	C19H13NO5	335.1	[16]
74	lakshminine	C17H12N2O2	276.1	[11]
75	menisoxoisoaporphine A	C24H26N2O4	406.2	[11]
76	daurioxoisoporphine B	C19H16N2O4	336.1	[17]
77	Menisoxoisoaporphine C	C27H24N2O4	440.2	[17]
78	tyraminoporphine	C27H24N2O5	456.2	[11]
79	daurioxoisoporphine A	C26H22N2O4	426.2	[7]
80	2,3-dihydrodauriporphine	C20H19NO5	353.1	[7]
81	dihydromenisporphine	C19H17NO4	323.1	[16]
82	sinotumine F	C18H15NO6	341.1	[7]
83	sinomenine	C19H23NO4	329.2	[6]
84	scrodentoside A	C19H23NO4	329.2	[11]
85	disinomenine	C38H44N2O8	656.3	[21]
86	dechloroacutumine	C19H25NO6	363.2	[5]
87	dauricumine	C19H24ClNO6	387.1	[5]
88	dauricumidine	C18H22ClNO6	383.1	[14]
89	acutumine	C19H24ClNO6	397.1	[5]
90	acutuminine	C19H24ClNO5	381.1	[14]
91	acutumidine	C18H22O6NCl	383.1	[14]
92	stopholidine	C19H21NO4	327.1	[4]
93	corydalmine	C20H23NO4	341.2	[7]
94	pessoine	C18H19NO4	313.1	[7]
95	cheilanthifoline	C19H19NO4	325.1	[7]
96	stepholidine	C19H21NO4	327.1	[7]
97	(+)-cheilanthifoline	C19H19NO4	325.1	[17]
98	epiberberine	C20H18NO4+	336.1	[14]
99	(6aS, 1′R)-apormenidaurine A	C44H46N2O7	714.3	[13]
100	(6aS, 1′S)-apormenidaurine B	C46H51N2O10	791.4	[13]
101	thalifoline	C11H13NO3	207.1	[7]
102	N-methylcorydaldine	C12H15NO3	221.1	[7]
103	corypalline	C11H15NO2	193.1	[7]
104	O-methylcorypalline	C12H17NO2	207.1	[7]
105	pycnarrhine	C11H14NO2+	192.1	[22]
106	amurolin	C19H25NO3	315.2	[22]
107	coclaurine	C17H19NO3	285.1	[7]
108	lotusine	C19H24NO3+	314.2	[7]
109	reticuline	C19H23NO4	329.2	[7]
110	(R)-6-methoxy-1-(4-methoxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol	C19H23NO3	313.2	[7]
111	pseudolaudanine	C20H25NO4	343.2	[7]
112	N-methylcoclaurine	C18H21NO3	299.2	[7]
113	armepavine	C19H23NO3	313.2	[7]
114	pecrassipine B	C26H27NO5	433.2	[7]
115	menidaurine A	C26H27NO5	433.2	[23]
116	menidaurine B	C27H29NO6	463.2	[23]
117	menidaurine C	C26H27NO5	433.2	[23]

: 1–45), apomorphins and oxidized isoapomorphins (Table 1: 46–82), morpholines (Table 1: 83–91), proberberberine and berberine (Table 1: 92–98), and other classes of alkaloids (Table 1: 99–117). Among them, bibenzylisoquinolines, apomorphins, and oxidized isoapomorphins alkaloids are the most distributed among the alkaloid components of M. Rhizoma.

2.1.1. Bisbenzylisoquinoline Alkaloids

Bisbenzylisoquinoline alkaloids contain two benzylisoquinolines linked by diphenyl ether, benzyl phenyl ether or biphenyl bonds [24]. The structural skeleton I of bisbenzylisoquinoline alkaloids from M. Rhizoma is shown in Figure 1, where the substituents R₁–R₅ are often H or CH₃. Alkaloids 1–36 belong to this category, where a mixture of multiple lipid-soluble alkaloids with alkaloids 1 and 4 as the main components is also known as Phenolic Alkaloids from Menisphermum dauricum (PAMD) [25]. There are several isomers in this structure due to the different C₁-H, C_1′-H and C₂-CH₃, C_2′-CH₃ space configurations, such as alkaloids 12 and 13, and the difference between them is the difference in the C₁-H space configuration. Since the structural changes within the molecules of this class of alkaloids are mainly in the number of aromatic oxygens, the number of ether bonds, the nature of oxygen bridges, the position of carbon-carbon bond initiation on the alkaloid units, and the nature of nitrogen atom substituents, these structural changes are highly likely to produce new structures of bisbenzylisoquinoline alkaloids and new skeletons [10]. The structural skeleton II, also shown in Figure 1, differs from the structural skeleton I by the change in the position of the connection between the two benzylisoquinolines. The C_7′ position in this structure is connected to the C₁₁ or C₁₂ position, and the C7 position is often connected to the C11′ or C12′ position by an oxygen bridge or replaced by OH or OCH₃, as in the C₅, C_5′, or C_8′ positions. All alkaloids 37–44 found in the extract of M. Rhizoma have this feature, with alkaloid 37 and alkaloid 44 being trace alkaloids obtained from M. Rhizoma for the first time. Compared with the typical bisbenzylisoquinoline structural skeleton I of M. Rhizoma, alkaloid 45 has a broken bond between the C_1′ and C_9′ positions and undergoes carbonylation to become a ring-cleaving bisbenzylisoquinoline structure. The bisbenzylisoquinoline alkaloids that have been identified in M. Rhizoma are shown in Figure 2 and Figure 3. In addition to the above bisbenzylisoquinoline alkaloids, Li et al. [7] identified four other bisbenzyltetrahydroisoquinoline alkaloids from M. Rhizoma with the help of the UPLC-Q-TOF-MS/MS technique, namely, N-demethylepiphylline, 2-demethylepiphylline, 5-hydroxylepiphylline, and tamsulosin.

2.1.2. Apomorphines and Oxidized Isoporphine Alkaloids

The alkaloids are based on a tetracyclic aromatic backbone formed by the oxidative coupling of the phenol of the benzylisoquinoline precursor [26]; the characteristic tetracyclic system (rings A–D), in which ring B often contains a nitrogen atom [24], is shown in Figure 4. In addition, the oxidized isoporphine alkaloids also have a four-ring system, which differs from the apomorphine alkaloids in the oxidation of the ring C methylene and the position of the linkage of ring D. The structural skeleton III is shown in Figure 4. The alkaloids 63–82 found in M. Rhizoma belong to this group of alkaloids, where alkaloid 82 differs from other oxidized iso-apomorphine alkaloids in M. Rhizoma by the breakage and oxidation of ring A to the carbonyl group and the reduction of ring C carbonyl group to the hydroxyl group. It should be noted that alkaloids 69, 70, and 72 are identified as the new compounds of oxidized isoporphine alkaloids [16,20]. Apomorphine alkaloids and oxidized isoporphine alkaloids have been identified in M. Rhizoma are shown in Figure 5 and Figure 6, respectively.

2.1.3. Morphine Alkaloids, Proberberberine, Berberine, and Other Alkaloids

The morphine alkaloids, proberberberine, and berberine alkaloids that have been extracted and isolated from M. Rhizoma are detailed in Figure 7 and Figure 8. Among them, alkaloids 87–91, which are chlorinated alkaloids with a new backbone, have been discovered in M. Rhizoma in recent years. In addition, the berberine alkaloid 98, derived from the n-butanol part of the 50% ethanol extract of M. Rhizoma, was found for the first time in the genus Batrachochia [14]. In addition to the above alkaloids, other classes of alkaloids currently found in M. Rhizoma are shown in Figure 9. Wei et al. [13] isolated apomorphine–benzylisoquinoline alkaloids 99 and 100 from M. Rhizoma, and other studies obtained simple isoquinoline alkaloids (alkaloids 101–106) and monobenzylisoquinoline alkaloids (alkaloids 107–117) from M. Rhizoma. Among them, Chen et al. [23] identified three newly discovered alkaloids 115–117 obtained in the dichlorinated carbon part of the 95% ethanol extract of M. Rhizoma as simple isoquinoline alkaloids by the nuclear magnetic resonance technique.

2.2. Other Components

In addition to alkaloids, M. Rhizoma contains volatile components, polysaccharides, quinones, cardiac glycosides, lactones, saponins, tannins, proteins, and resins, among other chemical constituents [21]. In recent years, some components isolated for the first time from Menispermaceae or Menispermum Linn. or M. Rhizoma have been discovered, greatly enriching the chemical composition of M. Rhizoma. Compounds 1 and 2 were isolated from the dichloromethane part of 50% ethanol extract of M. Rhizoma by Li et al. [14], where compound 1 was obtained for the first time from Menispermum Linn. Compounds 7–9, which are nephrotoxic, were first isolated from M. Rhizoma [4,5]; compounds 14–17, 19, 22 were first isolated from Menispermaceae; and compounds 12–23 were first isolated from Menispermum Linn. [27]. In addition, Ren et al. [28] analysed the composition of the fatty oil of M. Rhizoma by GC-MS; the specific components are shown in

Table 2. Other components in M. Rhizoma.

No.	Component	Formula	Mass	Reference
1	p-hydroxyphenethyltrans-ferulate	C18H18O5	314.1	[14]
2	daucosterol	C35H60O6	576.4	[14]
3	vanillin	C8H8O3	152.0	[5]
4	N-trans-feruloyltyramine	C18H19NO4	313.1	[5]
5	β-sitostenone	C30H52O	428.4	[5]
6	β-sitosterol	C30H52O	428.4	[5]
7	aristoloterpenate I	C32H31NO8	557.2	[5]
8	aristolochic acid	C17H11NO7	341.1	[4]
9	aristolactone	C15H20O2	232.1	[4]
10	eleutheroside d	C34H46O18	742.3	[4]
11	vanillic acid	C8H8O4	168.0	[27]
12	4-hydroxybenzaldehyde	C7H6O2	122.0	[27]
13	syringaldehyde	C9H10O4	182.1	[27]
14	2-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone	C7H6O2	226.1	[27]
15	methyl 4-hydroxyphenylacetate	C9H10O3	166.1	[27]
16	2-(4-hydroxyphenyl)-nitroethane	C8H9NO3	167.1	[27]
17	4-hydroxybenzyl cyanide	C8H7NO	133.1	[27]
18	dibutyl phthalate	C16H22O4	278.2	[27]
19	fragransin b2	C11H14O5	226.1	[27]
20	7-hydroxy-3,6-dimethoxy-1,4-phenanthraquinone	C16H12O5	284.1	[27]
21	palmitic acid	C16H32O2	256.2	[27]
22	arachidic acid	C20H40O2	312.3	[27]
23	β-stigmasterol	C29H48O	412.4	[27]
24	ethyl pentamethylbenzene	C13H26	182.2	[28]
25	tetradecane	C14H30	198.2	[28]
26	2,6,10-trimethylhexadecane	C17H36	240.3	[28]
27	octadecane	C18H38	254.3	[28]
28	diheptadecane	C27H56	380.4	[28]
29	methyldecanoate	C11H22O2	186.2	[28]
30	2,4-bis(1,1-dimethylethyl-)phenol	C14H28O	212.2	[28]
31	12-methyl-methyltridecanoate	C15H30O2	242.2	[28]
32	2-dodecen-1-yl(-1)succinic anhydride	C16H25O3	265.2	[28]
33	9-hexadecenoic acid	C16H30O2	254.2	[28]
34	2-methyl-1-hexadecanol	C17H24O	244.2	[28]
35	7-methyl-tetradecene(z)-1-ol acetate	C17H29O2	265.2	[28]
36	methylpalmitate	C17H34O2	270.3	[28]
37	14-methyl-methylhexadecanoate	C18H36O2	284.3	[28]
38	8,11-methyl-octadecadienoate	C19H32O2	292.2	[28]
39	methyllinoleate	C19H34O2	294.3	[28]
40	methyloleate	C19H36O2	296.3	[28]
41	methylstearate	C19H38O2	298.3	[28]
42	16-methyl-methylheptadecanoate	C19H38O2	298.3	[28]
43	methyleicosanoate	C21H42O2	326.3	[28]
44	20-methyl-methyldocosanoate	C22H44O2	340.3	[28]
45	isopropyl-5,6,19-dioctadecatrienoate	C31H56O2	460.4	[28]
46	2,2,2-trifluoroethyl-9-octadecadienoic acid	C20H33F3O2	362.2	[28]
47	2-2-amino-n-(3,4,4a,5,6,7-hexahydro-5,6,8-trihydroxy-3-methyl-1-oxo-1h-2-benzopyran-4-yl)-propanamide	C13H20N2O6	300.1	[28]
48	3-methylbenzyl alcohol, tert-butyldimethylsilyl ether	C14H30OSi	242.2	[28]
49	hexaethylcyclotrisiloxane	C12H30O3Si3	390.1	[28]
50	6,6,8,8,10,10-hexamethyl-2,5,7,9,11,14-hexaoxa-6,8,10-trisilicopentadecane	C12H32O6Si3	356.2	[28]
51	octamethylcyclotrisiloxane	C8H24O4Si4	296.1	[28]
52	decamethylcyclotrisiloxane	C10H30O5Si5	370.1	[28]
53	dodecamethylcyclotrisiloxane	C12H36O6Si6	444.1	[28]
54	tetradecamethylcyclotrisiloxane	C14H42O7Si7	518.1	[28]
55	hexadecamethylcyclotrisiloxane	C16H48O8Si8	592.2	[28]

, compounds 24–55. In addition to the above components, Lin et al. [29,30] also obtained one water-soluble polysaccharide WMDP with a triple-helix structure and two acidic polysaccharides MDP-A1 and MDP-A2 from M. Rhizoma.

3. Pharmacological Activities

A diverse and structurally complex group of alkaloids is one of the characteristics of the chemical composition of M. Rhizoma. In recent years, many scholars have conducted extensive research on the biological activities of alkaloids in M. Rhizoma, while the discoveries of other components of M. Rhizoma and their activities have also greatly enriched the material basis of the medicinal effects of M. Rhizoma. It has been found to play an important role in anti-tumour, anti-inflammatory, antioxidant, antibacterial, cardio-protective, anti-depressant, and anti-Alzheimer’s disease.

3.1. Anti-Tumour Effect

A network pharmacology-based study investigating the antihepatocarcinogenic mechanism of isoquinoline alkaloids concluded that tetrandrine could exert antihepatocarcinogenic effects by inducing cellular autophagy, inhibiting tumour cell invasion and metastasis, and enhancing radiosensitivity [31]. The results of another tumour cytotoxic activity test showed that thalifortine, cycleapeltine, sutchuenenine, and menisperine had good inhibitory activity on the proliferation of human hepatoma HepG2 cells [10]. PAMD, with dauricine and daurisoline as the main components, has been used as a broad-spectrum anti-tumour active ingredient in recent years. Recent studies have shown that PAMD can down-regulate the expression of Shh, Ptch1, Smo and Gli1, key loci of the Hedgehog signalling pathway, and inhibit the growth of tumour cells, thus achieving anti-tumour effects [32]. In addition, daurisoline was able to induce apoptosis in human hepatoma cells HepG2 and Hep3B, promote Hep3B cell necrosis, and inhibit the migration ability of hepatocellular carcinoma cells [33], while dauricine can exert anti-tumour effects by inhibiting the proliferation of SW1900 and BxPC-3 pancreatic cancer cells [34,35], Hela cervical cancer cells [36], Huh7 liver cancer cells [37], Eca-109 esophageal cancer cells [38], A375 and A2058 melanoma cells [39], kidney cancer cells [40], colon cancer cells [41], EJ-1 and 5637 bladder cancer cells [42], and CNE-2 nasopharyngeal cancer cells [43]. All the alkaloids mentioned above belong to the bisbenzylisoquinoline group of alkaloids, indicating the indispensable role of this group of alkaloids in the anti-tumour activity exerted by M. Rhizoma. In addition, studies have shown that morphine alkaloids acutumine are generally effective in inhibiting SMMC-7721 human liver cancer cells, MCF-7 human breast cancer cells, A549 human lung cancer cells, SW-480 human intestinal cancer cells, and HL-60 human leukemia cells [22]. A water-soluble polysaccharide WMDP with a triple-helix structure and two acidic polysaccharides MDP-A1 and MDP-A2 extracted from M. Rhizoma by Lin et al. [29,30] could significantly inhibit the proliferation of SKOV3 human ovarian cancer cells and effectively induce the apoptosis of SKOV3 cells, which indicated the potential application of the above polysaccharides as natural anti-tumour drugs and provided a scientific basis for the in-depth study of the active components of M. Rhizoma that exert anti-tumour effects.

3.2. Anti-Inflammatory Effect

Ulcerative colitis (UC)—characterized by abdominal pain; diarrhoea; and mucous, bloody stools as the main clinical manifestations—has a high recurrence rate and is difficult to cure [44]. Studies have shown that bisbenzylisoquinoline alkaloids dauricine, daurinoline, dauricinoline, daurisoline and tetrandrine, and morphine alkaloids sinomenine and acutumine can reduce the expression of MPO and COX-2, down-regulate the expression of NF-κB/TLR4 mRNA and significantly reduce the levels of TNF-α, IL-1β, and IL-6 in mouse colon tissues to varying degrees, suggesting that M. Rhizoma has anti-inflammatory and promotes the repair of damaged tissues in the colon [6]. Similar studies have demonstrated that in addition to lowering the serum levels of IL-6, MMP and VEGF levels are also down-regulated in the treatment of UC by northern bean root monosodium glutamate [45]. Network pharmacological studies on the mechanism of action of M. Rhizoma in the treatment of UC have demonstrated that M. Rhizoma may intervene in digestive and immune systems by participating in biological processes such as the regulation of cell proliferation and apoptosis; signalling; transcriptional regulation and drug response; and modulating pathways such as TNF, PI3K-Akt, T-cell receptor signalling, etc. The components involved in the drug-active ingredient-target network include morphine alkaloids dauricumine and acutuminine, and bisbenzylisoquinoline alkaloids stepharine, bianfugecine, and stepholidine [46]. In addition to a good effect of the active constituents in M. Rhizoma for the treatment of UC, the bisbenzylisoquinoline alkaloids (+)-1,3,4-dehydrocepharanthine, cissampentine A, cissampentine B and (−)-pseudocurine, apocynine alkaloid 6-acetyl-5,6-dihydro-1,2-dimethoxy-4H-dibenzo[de,g]-quinoline, oxidized isoapocynine alkaloids oxoisoaporphine B, menisoxoisoaporphine A, and daurioxoisoporphine B in M. Rhizoma showed good inhibitory activity against the release of NO from rat macrophages in the LPS-induced anti-inflammatory activity assay [11,17]. In another study, it was demonstrated that the total alkaloids of M. Rhizoma inhibit ovalbumin-induced airway inflammation in mice with asthma by reducing the concentrations of interleukin 4, 5, and 13, down-regulating the levels of TNF-α and eotax in bronchoalveolar lavage fluid, and inhibiting the increase in serum levels of total immunoglobulin E and ovalbumin-specific immunoglobulin E. The results of this experiment suggest that the total alkaloids of M. Rhizoma can inhibit ovalbumin-induced airway inflammation in mice by modulating T-helper 2 responses and chemokine levels, suggesting that the total alkaloids of M. Rhizoma may be potential anti-asthmatic agents [47]. In summary, the alkaloids of M. Rhizoma, especially bisbenzylisoquinoline and morphinane alkaloids, are the significant pharmacological bases for the anti-inflammatory activity of M. Rhizoma. In addition, arachidic acid obtained from the methanolic extract of M. Rhizoma by Ren et al. [27] showed a strong inhibition of NO and IL-6 release from RAW 264.7 cells, suggesting that it has good anti-inflammatory activity in vitro, which provides a scientific and theoretical basis for the subsequent search for new anti-inflammatory components of M. Rhizoma.

3.3. Antioxidant Effect

DPPH radicals are commonly used for in vitro antioxidant activity evaluation, and the stronger the scavenging ability of DPPH radicals, the stronger the antioxidant capacity. The scavenging rate of oxidized apomorphine alkaloids dauriporphine and menisporphine on DPPH radicals was similar to that of the positive reference drug vitamin C, both above 90%, providing an experimental basis for the development of antioxidant drugs from the alkaloids of M. Rhizoma [48]. In addition, Ren et al. [28] found that the fatty oil of M. Rhizoma also had a better scavenging ability for DPPH radicals with a scavenging rate of 70.1%; thus, it was speculated that the long-chain unsaturated fatty acid methyl esters such as methyllinoleate and methyloleate, which were more abundant in the fatty oil of M. Rhizoma identified by GC-MS, might be related to the antioxidant activity of the fatty oil of M. Rhizoma.

3.4. Antibacterial Effect

The alkaloid components of M. Rhizoma were reported to have inhibitory effects on a variety of respiratory and intestinal bacteria, with the most significant inhibitory effect on dauricine, with an inhibition rate of 83.33%, and the best inhibitory effect on S. pneumoniae [49]. Clinical studies further confirmed that dauricine also inhibited E. coli, S. aureus, and B. subtilis to different degrees, and the inhibitory effect was: B. subtilis > S. aureus > E. coli [50].

3.5. Cardio-Protective Effect

Dauricine is often used as a clinical treatment for hypertension and cardiac arrhythmias. Its antihypertensive effect was reported to be related to the antagonism of Ca²⁺ channels, and its antiarrhythmic mechanism of action is similar to that of the class III antiarrhythmic drug amiodarone: it mildly inhibits Ca²⁺-ATPase activity, decreases sarcoplasmic reticulum calcium uptake and has the effect of inhibiting Na⁺ inward flow, Ca²⁺ inward flow, and K⁺ outward flow, especially blocking K⁺ outward flow [51]. Ischemic cerebrovascular diseases such as ischemic stroke and stroke often lead to damage and disruption of the blood–brain barrier and accompanying cerebral edema. Establishing animal models of focal cerebral ischemia and reperfusion injury in the brain of rats is one of the most critical tools for studying the pathophysiological mechanisms of these cardiovascular diseases [52]. Zhang et al. [53] found that PAMD reduced the water content of brain tissue in this animal model of injury and reduced the permeability of blood–brain barrier, which was associated with the upregulation of the p-NR1 expression by PAMD and thus reduced the incidence of NMDAR activation. Additional studies have demonstrated that dauricine, one of the main components of PAMD, protects against ischaemia-reperfused brain tissue damage by inhibiting the expression of P-glycoprotein in brain tissue and achieving reverse retention of this alkaloid in brain tissue [52]. Other five oxidized isoporphine alkaloids showed good anti-myocardial ischaemic activity, with menisporphine, dauriporphinoline, and oxoisoaporphine A exhibiting a good anti-myocardial ischaemic effect by effectively increasing the survival of cardiomyocytes damaged by glyoxylate deprivation [20].

3.6. Anti-Hypoxic Effect

Shao et al. [4] found in the study of the anti-hypoxic activity of the chemical constituents of M. Rhizoma that the protective effect of bisbenzylisoquinoline and morphine alkaloids on hypoxia-injured EA.hy926 vascular endothelial cells were more obvious. The more abundant bisbenzylisoquinoline alkaloid daurisoline in M. Rhizoma showed the strongest anti-hypoxic activity, followed by morphine alkaloids acutumine and acutuminine. The above studies provide the material basis for the better anti-hypoxic activity of M. Rhizoma.

3.7. Anti-Depressant Effect

Depressed patients tend to have decreased levels of 5-hydroxytryptamine (5-HT), and certain genetic polymorphisms in 5-HT metabolism and transporters are associated with depression [54]. Studies have confirmed that 5-HT can be catabolized and deaminated by residual MAO-A in the capillaries [54]. Several synthetic dihydro and oxo-isoporphine derivatives were evaluated by in vitro experiments, and the results showed that all dihydro and oxo-isoporphine derivatives tested were selective MAO-A inhibitors, with the most representative and potent in vitro MAO-A inhibitor being 5-methoxyoxoisoaporphine (OXO4), an oxo-isoporphine derivative synthesized from M. Rhizoma [55]. The compulsive swimming trial added to the evidence that OXO4 requires a smaller dose for the same duration of action to achieve the same antidepressant effect compared to classical antidepressants [55]. Based on these facts, the oxidized isoporphine alkaloids in M. Rhizoma are expected to be developed as more efficient antidepressants.

3.8. Anti-Alzheimer’s Disease Effect

One of the primary pathogeneses of Alzheimer’s disease (AD) that is now widely recognized is its association with impairment in cholinergic transmission processes, where patients with low acetylcholine levels and reduced function in the brain experience significant cognitive impairment. The results of in vitro enzyme activity experiments showed that the alkaloids in M. Rhizoma inhibited acetylcholinesterase (AChE), with the monobenzylisoquinoline alkaloid pecrassipine B having the most significant inhibitory effect on AChE, followed by that of the bisbenzylisoquinoline alkaloid daurisoline, the morpholino alkaloid acutumine, the simpleisoquinoline alkaloid thalifoline, pycnarrhine, and amurolin; the inhibition effect of the simpleisoquinoline alkaloid corypalline is weaker in comparison. The molecular docking results showed that the strength of AChE inhibition by pecrassipine B and corypallinewas was related to their respective molecular structures and the degree of AChE binding [22]. Neurotoxic amyloid β-protein (Aβ) is a major component of neuroinflammatory plaques. Related studies have demonstrated that Aβ exerts neurotoxic effects and induces neuronal apoptosis by increasing the expression level of the pro-apoptotic gene Bax, decreasing that of the anti-apoptotic gene Bcl-2 [56]. It has also been shown that dauricine can significantly reduce the levels of IL-1β, IL-6, RAGE, and NF-κBp65 in the hippocampus of mice and decrease Aβ accumulation, thus delaying the course of AD [57]. Two other research results provided new ideas for the treatment of AD with M. Rhizoma: Wang [58] used the Nrf2/Keap1 antioxidant pathway to verify that dauricine could significantly increase the expression level of Nrf2, a key antioxidant factor, and then used the antioxidant effect of dauricine to repair damaged cells using Aβ aggregation as a therapeutic target; the results demonstrated that dauricine could be brain-targeted for the treatment of AD. A similar study in which dauricine was applied to an AD transgenic cell model resulted in a gradual increase or decrease in cell survival and MDA content and a gradual decrease in COX-2 protein expression in the AD transgenic model, demonstrating the protective effect of dauricine against oxidative damage in this model [59]. In summary, it is reasonable to assume that the isoquinoline alkaloids in M. Rhizoma are potentially promising for the prevention and treatment of AD.

3.9. Toxicity

M. Rhizoma is slightly toxic and clinical application is accompanied by adverse effects such as nausea, vomiting, loss of appetite, dyspepsia, bloating, and diarrhoea. Studies have shown that the acute toxicity of the alcoholic fraction of M. Rhizoma is greater than that of the aqueous fraction [60], and the total alkaloids of M. Rhizoma are the major alcohol-soluble components, thus verifying the studies on the chemical composition of M. Rhizoma reported in the literature [61]. This suggests that the alkaloids contained in M. Rhizoma are the main material basis for its toxicity. The toxic effects of the aqueous and alcoholic fractions of M. Rhizoma manifested as acute or chronic hepatotoxic injury with significant changes in serum ALT, AST, and hepatic body ratios [62]. Similar studies have further confirmed that the water and alcohol extraction of M. Rhizoma can increase MDA content in liver tissue and decrease SOD activity; this confirms, at the intrahepatic substance level, that the mechanism of hepatotoxic injury caused by M. Rhizoma is related to the induction of lipid peroxidation and reduction of its own redox capacity after causing oxidative stress in the body, as well as to the NO-mediated damage pathway [62].

4. Conclusions

With a wide distribution range and abundant medicinal resources, M. Rhizoma has a long history of medicinal use. In recent years, domestic and foreign scholars have conducted extensive and in-depth studies on the chemical components of M. Rhizoma, especially alkaloid components, and up to now, more than 150 chemical components, including 117 alkaloids, have been identified from M. Rhizoma. Among the alkaloid components of M. Rhizome, bisbenzylisoquinolines are predominant, and apomorphines and oxidized isoporphines are the next most abundant; the effects of M. Rhizoma in anti-tumour, antioxidant, anti-inflammatory, antibacterial, cardiovascular and cerebrovascular protection, anti-depressant, and anti-Alzheimer’s disease have been gradually confirmed and applied in the treatment of clinical diseases. The above research results have carried forward the modernization of traditional medicines. To summarize the current results, three points need attention for further research on M. Rhizoma: Firstly, in the pharmacological research on the alkaloid components of M. Rhizoma, most of the studies focused on the PAMD and relatively few studies on other alkaloids. Compared with the current research, the pharmacological studies of other chemical components isolated from M. Rhizoma are relatively lacking. Thirdly, the pharmacological study on M. Rhizoma can also be combined with the knowledge of molecular biology, proteomics, metabolomics, and other disciplines to investigate further the targets, mechanisms, and metabolic patterns of its effects. This paper reviews the progress of research on the chemical composition and pharmacological effects of M. Rhizoma in recent years and provides a basis for the further development and utilization of M. Rhizoma.