Natural Products and Their Applications in Pharmaceutical, Nutritional and Cosmetic Products

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Pharmaceutical Science".

Deadline for manuscript submissions: closed (25 August 2023) | Viewed by 33226

Special Issue Editors


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Guest Editor
Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy
Interests: cosmetics; natural compound; antimicrobial; cosmeto-food; characterization; formulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural products were the first source of nutritional, pharmaceutical, and cosmeceutical molecules for human health. Notwithstanding the important discoveries in the field of synthetic (chemical and biotechnological) molecules, natural products still represent an unavoidable source of molecular diversity and are of particular use both on their own and for the creation of novel synthetic compounds. Furthermore, the increasing concern regarding environmental pollution and the awareness that nature is humanity’s ally and should not be challenged by polluting it with molecules not already present in nature have led to a continuous and steady increase in the consumption of natural and organic products compared to those from synthetics. A sustainable answer must be given to the question of how to tackle a growing demand, as otherwise, the use of natural products would be unethical. For these reasons, we believe it is of great importance to develop approaches, molecules, or derived products using an advanced scientific approach that considers the traditional use, but enhancing it in the light of the most advanced technologies available today.

Prof. Dr. Stefano Manfredini
Prof. Dr. Silvia Vertuani
Guest Editors

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Keywords

  • natural
  • pharmaceutical
  • nutraceutical
  • cosmeceutical
  • isolation
  • characterization
  • preparation
  • evaluation

Published Papers (12 papers)

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Research

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15 pages, 2365 KiB  
Article
pH-Dependence Cytotoxicity Evaluation of Artepillin C against Tumor Cells
by Wallance M. Pazin, Renata R. Miranda, Karina A. Toledo, Frank Kjeldsen, Carlos J. L. Constantino and Jonathan R. Brewer
Life 2023, 13(11), 2186; https://doi.org/10.3390/life13112186 - 9 Nov 2023
Cited by 1 | Viewed by 5400
Abstract
Brazilian green propolis is a well-known product that is consumed globally. Its major component, Artepillin C, showed potential as an antitumor product. This study explored the impact of Artepillin C on fibroblast and glioblastoma cell lines, used as healthy and very aggressive tumor [...] Read more.
Brazilian green propolis is a well-known product that is consumed globally. Its major component, Artepillin C, showed potential as an antitumor product. This study explored the impact of Artepillin C on fibroblast and glioblastoma cell lines, used as healthy and very aggressive tumor cell lines, respectively. The focus of the study was to evaluate the pH-dependence of Artepillin C cytotoxicity, since tumor cells are known to have a more acidic extracellular microenvironment compared to healthy cells, and Artepillin C was shown to become more lipophilic at lower pH values. Investigations into the pH-dependency of Artepillin C (6.0–7.4), through viability assays and live cell imaging, revealed compelling insights. At pH 6.0, MTT assays showed the pronounced cytotoxic effects of Artepillin C, yielding a notable reduction in cell viability to less than 12% among glioblastoma cells following a 24 h exposure to 100 µM of Artepillin C. Concurrently, LDH assays indicated significant membrane damage, affecting approximately 50% of the total cells under the same conditions. Our Laurdan GP analysis suggests that Artepillin C induces autophagy, and notably, provokes a lipid membrane packing effect, contributing to cell death. These combined results affirm the selective cytotoxicity of Artepillin C within the acidic tumor microenvironment, emphasizing its potential as an effective antitumor agent. Furthermore, our findings suggest that Artepillin C holds promise for potential applications in the realm of anticancer therapies given its pH-dependence cytotoxicity. Full article
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15 pages, 3314 KiB  
Article
Up-Cycling of Olea europaea L. Ancient Cultivars Side Products: Study of a Combined Cosmetic–Food Supplement Treatment Based on Leaves and Olive Mill Wastewater Extracts
by Raissa Buzzi, Irene Gugel, Stefania Costa, Sonia Molesini, Silvia Boreale, Erika Baldini, Nicola Marchetti, Silvia Vertuani, Patrizia Pinelli, Silvia Urciuoli, Anna Baldisserotto and Stefano Manfredini
Life 2023, 13(7), 1509; https://doi.org/10.3390/life13071509 - 5 Jul 2023
Cited by 2 | Viewed by 1212
Abstract
In recent years, a reversal of the global economic framework has been taking place: from the linear model, there has been a gradual transition to a circular model where by-products from the agri-food industry are taken and transformed into value products (upcycling) rather [...] Read more.
In recent years, a reversal of the global economic framework has been taking place: from the linear model, there has been a gradual transition to a circular model where by-products from the agri-food industry are taken and transformed into value products (upcycling) rather than being disposed of. Olive tree pruning represents an important biomass currently used for combustion; however, the leaf part of the olive tree is rich in phenolic substances, including hydroxytyrosol. Mill wastewater is also discarded, but it still contains high amounts of hydroxytyrosol. In this study, cosmetic and food supplement formulations were prepared using biophenols extracted from leaves and wastewater and were tested in a placebo-controlled study on healthy volunteers using a combined cosmetic and food supplement treatment. A significant improvement in skin health indicators (collagen density, elasticity, etc.) and a 17% improvement against Photo-induced Irritative Stimulus was observed. Full article
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20 pages, 9254 KiB  
Article
In Vitro Antioxidant and Fibroblast Migration Activities of Fractions Eluded from Dichloromethane Leaf Extract of Marantodes pumilum
by Abbirami Balachandran, Stepfanie N. Siyumbwa, Gabriele R. A. Froemming, Morak-Młodawska Beata, Jeleń Małgorzata, Charlie A. Lavilla, Jr., Merell P. Billacura and Patrick N. Okechukwu
Life 2023, 13(6), 1409; https://doi.org/10.3390/life13061409 - 17 Jun 2023
Cited by 1 | Viewed by 1591
Abstract
(1) The complexity of diabetes and diabetic wound healing remains a therapeutic challenge because proper and systematic wound care and management are essential to prevent chronic microbial infection and mechanical damage to the skin. Marantodes pumilum, locally known as ‘Kacip Fatimah’, is [...] Read more.
(1) The complexity of diabetes and diabetic wound healing remains a therapeutic challenge because proper and systematic wound care and management are essential to prevent chronic microbial infection and mechanical damage to the skin. Marantodes pumilum, locally known as ‘Kacip Fatimah’, is an herb that has been previously reported to possess anti-inflammatory, analgesic, antinociceptive and antipyretic properties. The current study aims to assess the antioxidant and fibroblast cell migration activities of the fractions eluded from the dichloromethane extract of M. pumilum leaves. (2) The total antioxidant capacity of M. pumilum was assessed using the total proanthocyanidins and phosphomolybdenum assays, while DPPH, nitric oxide, hydrogen peroxide and superoxide free radical scavenging assays were tested to determine the antioxidant potential of M. pumilum. An in vitro scratch wound assay was performed to measure the fibroblast cell migration rate using normal and insulin-resistant human dermal fibroblast cells. (3) All M. pumilum fractions exhibited good antioxidant and fibroblast cell migration activity, among which fractions A and E displayed the greatest effect. (4) M. pumilum’s fibroblast migration activity could be attributed to its strong antioxidant properties along with its previously reported properties. Full article
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16 pages, 2740 KiB  
Article
Inhibitory Effects of Caulerpa racemosa, Ulva intestinalis, and Lobophora challengeriae on Tyrosinase Activity and α-MSH-Induced Melanogenesis in B16F10 Melanoma Cells
by Pradtana Choosuwan, Jantana Praiboon, Korawinwich Boonpisuttinant, Anirut Klomjit, Narongrit Muangmai, Rapeeporn Ruangchuay and Anong Chirapart
Life 2023, 13(4), 934; https://doi.org/10.3390/life13040934 - 3 Apr 2023
Cited by 3 | Viewed by 1877
Abstract
Melanogenesis involves a synthesis of melanin pigment and is regulated by tyrosinase. The addition of whitening agents with tyrosinase-inhibiting properties in cosmetics is becoming increasingly important. In this study, the ethanolic extracts from twelve seaweeds were assessed for tyrosinase-inhibiting activity using mushroom tyrosinase [...] Read more.
Melanogenesis involves a synthesis of melanin pigment and is regulated by tyrosinase. The addition of whitening agents with tyrosinase-inhibiting properties in cosmetics is becoming increasingly important. In this study, the ethanolic extracts from twelve seaweeds were assessed for tyrosinase-inhibiting activity using mushroom tyrosinase and melanin synthesis in B16F10 melanoma cells. The highest mushroom tyrosinase inhibition (IC50) was observed with Lobophora challengeriae (0.15 ± 0.01 mg mL−1); treatment was more effective than kojic acid (IC50 = 0.35 ± 0.05 mg mL−1), a well-known tyrosinase inhibitor. Three seaweeds, Caulerpa racemosa, Ulva intestinalis, and L. challengeriae, were further investigated for their ability to reduce melanogenesis in B16F10 cells. The ethanolic extracts of C. racemosa, U. intestinalis, and L. challengeriae showed inhibitory effects by reducing melanin and intracellular tyrosinase levels in B16F10 cells treated with α-melanocyte stimulating hormone in a dose-dependent manner. C. racemosa (33.71%) and L. challengeriae (36.14%) at 25 µg mL−1 reduced melanin production comparable to that of kojic acid (36.18%). L. challengeriae showed a stronger inhibition of intracellular tyrosinase (decreased from 165.23% to 46.30%) than kojic acid (to 72.50%). Thus, ethanolic extracts from C. racemosa, U. intestinalis, and L. challengeriae can be good sources of natural tyrosinase inhibitors and therapeutic or cosmetic agents in the future. Full article
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13 pages, 2730 KiB  
Article
Amentoflavone-Enriched Selaginella rossii Protects against Ultraviolet- and Oxidative Stress-Induced Aging in Skin Cells
by Hwa Lee, Soo-Yong Kim, Sang Woo Lee, Sehan Kwak, Hulin Li, Renzhe Piao, Ho-Yong Park, Sangho Choi and Tae-Sook Jeong
Life 2022, 12(12), 2106; https://doi.org/10.3390/life12122106 - 14 Dec 2022
Cited by 3 | Viewed by 2330
Abstract
Selaginellaceae plants are used in cosmetics to limit skin aging. This study is the first to investigate the anti-aging effects of Selaginella rossii (SR) on ultraviolet B (UVB)- and oxidative stress-induced skin cells. The 95% ethanol extract of Selaginella rossii (SR95E) contained much [...] Read more.
Selaginellaceae plants are used in cosmetics to limit skin aging. This study is the first to investigate the anti-aging effects of Selaginella rossii (SR) on ultraviolet B (UVB)- and oxidative stress-induced skin cells. The 95% ethanol extract of Selaginella rossii (SR95E) contained much higher amounts of amentoflavone (AMF), an active compound, than other Selaginellaceae plants and was more effective in inhibiting matrix metalloproteinase (MMP)-1 expression in CCD-986sk fibroblasts. SR95E significantly decreased UVB-induced MMP-1, MMP-2, MMP-3 and MMP-9 expression and enhanced procollagen type I C-peptide content and mRNA expression of collagen type I alpha (COL1A)1 and COL1A2 in CCD-986sk fibroblasts. In HaCaT keratinocytes, SR95E treatment also dose-dependently decreased UVB-induced MMP-1 concentration and MMP-1, MMP-2, MMP-3 and MMP-9 mRNA expression. Moreover, SR95E treatment markedly inhibited UVB-induced c-Jun N-terminal kinase and p38 mitogen-activated protein kinase signaling and nuclear factor kappa-B signaling in HaCaT cells. Furthermore, SR95E and AMF markedly regulated the 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced expression of cellular senescence-related markers, including p16, p21 and LMNB1, in HaCaT cells. Overall, this study indicates that SR may have potential as a functional material on preventing UVB- and AAPH-induced skin aging and wrinkles. Full article
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13 pages, 4156 KiB  
Article
Ameliorative Effect of D-Carvone against Hepatic Ischemia-Reperfusion-Induced Injury in Rats
by Maged E. Mohamed and Nancy S. Younis
Life 2022, 12(10), 1502; https://doi.org/10.3390/life12101502 - 27 Sep 2022
Cited by 3 | Viewed by 1603
Abstract
Background: D-carvone is a monoterpene that exists in the essential oils of several plant species. Hepatic ischemia-reperfusion (Hep I/R) takes place clinically during different scenarios of liver pathologies. The aim of the current investigation is to disclose the hepato-protective actions of carvone against [...] Read more.
Background: D-carvone is a monoterpene that exists in the essential oils of several plant species. Hepatic ischemia-reperfusion (Hep I/R) takes place clinically during different scenarios of liver pathologies. The aim of the current investigation is to disclose the hepato-protective actions of carvone against Hep I/R-induced damage and to reveal the underlying mechanism. Material and methods: Rats were assigned into five groups: sham and carvone plus sham groups, in which rats were administered either saline or carvone orally for three weeks prior to the induction of Hep I/R. In the Hep I/R group, rats were administered saline orally prior to the Hep I/R induction operation. The carvone 25 plus Hep I/R and Carvone 50 plus Hep I/R groups were administered carvone (25 and 50 mg/kg, respectively) for three weeks, followed by the induction of Hep I/R. Results: Liver ischemic animals demonstrated impaired liver function, several histopathological variations, and reduced levels of antioxidant enzyme activities. Furthermore, the Hep I/R groups showed the elevated gene expression of high-mobility group box 1 (HMGB1), toll-like receptors 4 (TLR4), nuclear factor kappa B (NFκB), and LR family pyrin domain containing 3 (NLP3), with subsequent escalated adhesion molecule 1 (ICAM-1), neutrophil infiltration, and several inflammatory mediators, including interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α), as well as apoptotic markers. Pretreatment with D-carvone alleviated ischemia/reperfusion-induced impaired liver function, diminished the histopathological deviations, and augmented the antioxidant enzymes. In addition, D-carvone mitigated the gene expression of HMGB1, TLR4, NFκB, and NLP3, with a subsequent reduction in ICAM-1, neutrophils infiltration, inflammatory mediators, and apoptotic markers. Conclusion: Rats pretreated with D-carvone exhibited hepato-protective actions against Hep I/R-induced damage via the downregulation of HMGB1, TLR4, NFκB, NLP3, associated inflammatory mediators, and apoptotic markers. Full article
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11 pages, 1856 KiB  
Article
Persicaria minor (Huds.) Opiz Prevents In Vitro Atherogenesis by Attenuating Tumor Necrosis Factor-α-Induced Monocyte Adhesion to Human Umbilical Vein Endothelial Cells
by Adila A. Hamid, Amilia Aminuddin, Nur Najmi Mohamad Anuar, Nur Izzati Mansor, Mohd Faizal Ahmad, Mohammed S. M. Saleh, Mohd Helmy Mokhtar and Azizah Ugusman
Life 2022, 12(10), 1462; https://doi.org/10.3390/life12101462 - 20 Sep 2022
Cited by 6 | Viewed by 1649
Abstract
Persicaria minor (Huds.) Opiz is an herb with anti-inflammatory, antioxidant, and anti-atherosclerosis effects. Nevertheless, the mechanism underlying its anti-atherosclerosis effect is poorly comprehended. This in vitro study assessed the protective effects of standardized aqueous extract of P. minor leaves (PM) on tumor necrosis [...] Read more.
Persicaria minor (Huds.) Opiz is an herb with anti-inflammatory, antioxidant, and anti-atherosclerosis effects. Nevertheless, the mechanism underlying its anti-atherosclerosis effect is poorly comprehended. This in vitro study assessed the protective effects of standardized aqueous extract of P. minor leaves (PM) on tumor necrosis factor-α (TNF-α)-induced monocyte adhesion to human umbilical vein endothelial cells (HUVEC), which is one of the pivotal early steps in atherogenesis. The results showed that PM decreased the mRNA and protein expression of cellular adhesion molecules, vascular adhesion molecule-1 and intercellular adhesion molecule-1, resulting in reduced adhesion of monocytes to HUVEC. Additionally, PM inhibited nuclear factor kappaB (NF-κB) activation as indicated by reduced NF-κB p65 levels in TNF-α-induced HUVEC. Overall, PM could prevent in vitro atherogenesis by inhibiting NF-κB activation and adhesion of monocytes to HUVEC. The effects of PM are probably mediated by its bioactive compound, quercetin-3-O-glucuronide. The findings may provide a rationale for the in vivo anti-atherosclerosis effect of PM, and support its potential use in atherosclerosis. Full article
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13 pages, 2829 KiB  
Article
Suppression of Pepper mild mottle virus (PMMoV) by Modified Whey Proteins
by Mohsen Mohamed Elsharkawy, Abdulaziz A. Al-Askar, Ahmed Abdelkhalek, Said I. Behiry, Muhammad Kamran and Mostafa Ali
Life 2022, 12(8), 1165; https://doi.org/10.3390/life12081165 - 30 Jul 2022
Cited by 4 | Viewed by 2021
Abstract
Modified whey proteins with quercetin (WPI-QU) and onion extract (WPI-OE), as a control approach, could be applicable because it is available, safe and cheap. The modified whey protein isolate (WPI) with quercetin dihydrate and onion extract powder rich with quercetin were evaluated for [...] Read more.
Modified whey proteins with quercetin (WPI-QU) and onion extract (WPI-OE), as a control approach, could be applicable because it is available, safe and cheap. The modified whey protein isolate (WPI) with quercetin dihydrate and onion extract powder rich with quercetin were evaluated for induction of systemic resistance against Pepper mild mottle virus (PMMoV) in pepper plants. Data of mass spectrometry illustrated that one or more of Qu isomers covalently attached to WPI. Unmodified whey protein (UWPI), WPI-QU and WPI-OE significantly decreased PMMoV concentration and severity at two weeks after inoculation. Plant height, number of leaves, and shoot fresh and dry weights were substantially increased in WPI-QU- and WPI-OE-treated pepper plants compared to the control. Total antioxidant status (TAS) and vitamin C contents were highly increased in WPI-OE-treated plants compared with other treatments. The expression levels of defense related genes (PR4, PR9, TIN1 and PIN2) were enormously elevated in WPI-OE and WPI-QU treatments using qRT-PCR. In conclusion, the results give novel insights to possible applications of the WPI–quercetin bioconjugates in designing a wide range of functional products. Moreover, this study is the first to establish the effective control of PMMoV by modified whey proteins. Full article
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15 pages, 5801 KiB  
Article
Resistance Induction and Direct Antifungal Activity of Some Monoterpenes against Rhizoctonia solani, the Causal of Root Rot in Common Bean
by Aly Derbalah, Asmaa Mohamed Shebl, Samah Fawzy Elgobashy, Abdelmonim Ali Ahmad, Noha Eldesoky Ramadan, Said I. Behiry, Ahmed Abdelkhalek, Muhammad Hamzah Saleem, Abdulaziz A. Al-Askar, Muhammad Kamran and Mohsen Mohamed Elsharkawy
Life 2022, 12(7), 1040; https://doi.org/10.3390/life12071040 - 12 Jul 2022
Cited by 9 | Viewed by 2016
Abstract
This study was conducted to evaluate eco-friendly control agents (carvone, cuminaldehyde, and linalool) against Rhizoctonia solani, which causes root rot disease either by induction of defense response or direct antifungal activity. The induction of resistance was examined by detecting the transcription of defense [...] Read more.
This study was conducted to evaluate eco-friendly control agents (carvone, cuminaldehyde, and linalool) against Rhizoctonia solani, which causes root rot disease either by induction of defense response or direct antifungal activity. The induction of resistance was examined by detecting the transcription of defense genes and the effect of the tested control agents on the growth and the yield of common bean plants. The growth of R. solani was significantly inhibited after treatment with the tested compounds compared to the untreated control under laboratory conditions. The disease severity of root rot was decreased in common bean plants treated with the tested compounds compared to untreated control plants under greenhouse conditions. Common bean plants treated with the tested control agents expressed defense genes (Phenylalanine ammonia lyase and β-1,3-Glucanase) involved in jasmonic acid (JA) and salicylic acid (SA) signaling pathways with 2–5 fold higher than the control. Treatment of common beans with the tested control agents and fungicide significantly improved the growth and yield characteristics of common bean. Therefore, the use of monoterpenes could be a novel strategy to control this pathogen and consider the first report. Full article
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10 pages, 5173 KiB  
Article
Evaluation of the Effect of Wheat Germ Oil and Olmutinib on the Thioacetamide-Induced Liver and Kidney Toxicity in Mice
by Salman Alamery, Seema Zargar, Fatimah Yaseen, Tanveer A. Wani and Abdulaziz Siyal
Life 2022, 12(6), 900; https://doi.org/10.3390/life12060900 - 15 Jun 2022
Cited by 10 | Viewed by 2152
Abstract
Thioacetamide (TAA) intoxication produces a reproducible standard animal model of induced liver and kidney injuries where free radicals are produced by phase I oxidation reactions, which eventually leads to liver and kidney failure. Wheat germ oil (WGO) is a unique food supplement with [...] Read more.
Thioacetamide (TAA) intoxication produces a reproducible standard animal model of induced liver and kidney injuries where free radicals are produced by phase I oxidation reactions, which eventually leads to liver and kidney failure. Wheat germ oil (WGO) is a unique food supplement with concentrated nutrient efficiency and has remarkable antioxidant functions. Olmutinib, on the other hand, is a chemotherapy drug considered safe for kidneys and the liver. Therefore, in this study, WGO and olmutinib were investigated for their effect on TAA-induced liver and kidney damage. Inflammatory markers; interleukin-1 beta (IL-1β); IL-6; and the levels of enzymatic markers ALT (Alanine aminotransferase), AST (Aspartate aminotransferase), LDH (Lactate dehydrogenase), and CK (creatinine kinase) in serum for liver and kidney were analyzed and evaluated along with histopathological changes in the tissue. Thirty male mice 4–6 weeks of age were grouped into five groups of six animals: the control group (saline) and the other groups (Groups II to V), which were given thioacetamide for two weeks. In addition, Group II continued with TAA; Group III was given olmutinib (30 mg/kg), Group IV was given the wheat germ oil (WGO) (1400 mg/kg), and Group V was given (olmutinib (30 mg/kg) + WGO (1400 mg/kg)) for five days. The results suggested that olmutinib treatment potentiated TAA-induced liver and kidney injury. At the same time, WGO efficiently alleviated TAA and TAA–olmutinib toxicity in Groups IV and V. The histological studies also showed reduced damage with WGO in the animal model. Hence, it was concluded that WGO could significantly reduce liver and kidney damage caused by TAA and olmutinib in mice. Full article
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Review

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18 pages, 709 KiB  
Review
The Molecular Mechanism of Natural Products Activating Wnt/β-Catenin Signaling Pathway for Improving Hair Loss
by Dong Wook Shin
Life 2022, 12(11), 1856; https://doi.org/10.3390/life12111856 - 11 Nov 2022
Cited by 12 | Viewed by 7040
Abstract
Hair loss, or alopecia, is a dermatological disorder that causes psychological stress and poor quality of life. Drug-based therapeutics such as finasteride and minoxidil have been clinically used to treat hair loss, but they have limitations due to their several side effects in [...] Read more.
Hair loss, or alopecia, is a dermatological disorder that causes psychological stress and poor quality of life. Drug-based therapeutics such as finasteride and minoxidil have been clinically used to treat hair loss, but they have limitations due to their several side effects in patients. To solve this problem, there has been meaningful progress in elucidating the molecular mechanisms of hair growth and finding novel targets to develop therapeutics to treat it. Among various signaling pathways, Wnt/β-catenin plays an essential role in hair follicle development, the hair cycle, and regeneration. Thus, much research has demonstrated that various natural products worldwide promote hair growth by stimulating Wnt/β-catenin signaling. This review discusses the functional role of the Wnt/β-catenin pathway and its related signaling molecules. We also review the molecular mechanism of the natural products or compounds that activate Wnt/β-catenin signaling and provide insights into developing therapeutics or cosmeceuticals that treat hair loss. Full article
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Other

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18 pages, 1376 KiB  
Systematic Review
Alpha-Phellandrene and Alpha-Phellandrene-Rich Essential Oils: A Systematic Review of Biological Activities, Pharmaceutical and Food Applications
by Matteo Radice, Andrea Durofil, Raissa Buzzi, Erika Baldini, Amaury Pérez Martínez, Laura Scalvenzi and Stefano Manfredini
Life 2022, 12(10), 1602; https://doi.org/10.3390/life12101602 - 14 Oct 2022
Cited by 13 | Viewed by 2733
Abstract
Alpha-phellandrene is a very common cyclic monoterpene found in several EOs, which shows extensive biological activities. Therefore, the main focus of the present systematic review was to provide a comprehensive and critical analysis of the state of the art regarding its biological activities [...] Read more.
Alpha-phellandrene is a very common cyclic monoterpene found in several EOs, which shows extensive biological activities. Therefore, the main focus of the present systematic review was to provide a comprehensive and critical analysis of the state of the art regarding its biological activities and pharmaceutical and food applications. In addition, the study identified essential oils rich in alpha-phellandrene and summarized their main biological activities as a preliminary screening to encourage subsequent studies on their single components. With this review, we selected and critically analyzed 99 papers, using the following bibliographic databases: PubMed, SciELO, Wiley and WOS, on 8 July 2022. Data were independently extracted by four authors of this work, selecting those studies which reported the keyword “alpha-phellandrene” in the title and/or the abstract, and avoiding those in which there was not a clear correlation between the molecule and its biological activities and/or a specific concentration from its source. Duplication data were removed in the final article. Many essential oils have significant amounts of alpha-phellandrene, and the species Anethum graveolens and Foeniculum vulgare are frequently cited. Some studies on the above-mentioned species show high alpha-phellandrene amounts up to 82.1%. There were 12 studies on alpha-phellandrene as a pure molecule showed promising biological functions, including antitumoral, antinociceptive, larvicidal and insecticidal activities. There were 87 research works on EOs rich in alpha-phellandrene, which were summarized with a focus on additional data concerning potential biological activities. We believe this data is a useful starting point to start new research on the pure molecule, and, in particular, to distinguish between the synergistic effects of the different components of the OEs and those due to alpha-phellandrene itself. Toxicological data are still lacking, requiring further investigation on the threshold values to distinguish the boundary between beneficial and toxic effects, i.e., mutagenic, carcinogenic and allergenic. All these findings offer inspiration for potential applications of alpha-phellandrene as a new biopesticide, antimicrobial and antitumoral agent. In particular, we believe our work is of interest as a starting point for further studies on the food application of alpha-phellandrene. Full article
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