PMID: 

Phytother Res. 2018 Oct ;32(10):1933-1949. Epub 2018 Jul 17. PMID: 30015401

Abstract Title: 

Silybum marianum (milk thistle) and its main constituent, silymarin, as a potential therapeutic plant in metabolic syndrome: A review.

Abstract: 

Metabolic syndrome describes a complex metabolic risk factors including obesity, hypertension, dyslipidemia, and diabetes. This syndrome is diagnosed by medical conditions such as weight gain, high blood pressure, high blood glucose, and disturbance in lipid profile. Metabolic syndrome has become as an important and increasing global health problem, so finding potentially novel solutions with less adverse effects is favorable for health problems. Herbal therapy plays an important role for treatment of different diseases. Silybum marianum is a plant that is used for centuries as a herbal treatment in liver and biliary tract diseases. Silymarin is the main component of S. marianum and derived from fruits and seeds of S. marianum (milk thistle). S. marianum has been found to exhibit antioxidant, lipid-lowering, antihypertensive, antidiabetic, antiatherosclerotic, anti-obesity, and hepatoprotective effects. Therefore, the aim of this review is to summarize different animal and human studies regarding the effect of S. marianum in metabolic syndrome and to identify the underlying mechanisms of action.

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PMID: 

J Pharm Bioallied Sci. 2019 Dec ;11(Suppl 4):S556-S561. Epub 2019 Dec 30. PMID: 32148363

Abstract Title: 

Anticalculi Activity of Apigenin and Celery (L.) Extract in Rats Induced by Ethylene Glycol-Ammonium Chloride.

Abstract: 

Objective: Kidney stones (nephrolithiasis) is one of the kidney diseases in the form of stones that contain crystal and organic matrix components. It is one of the most common diseases of the urinary tract. Calcium stone is the most important type of stone (80%) found in the case of kidney stones. Celery (L.) is a plant rich in flavonoids, which can break down calcium crystals. Apigenin is considered to be one of the main flavonoids because of its presence and abundance in celery. This research aimed to compare the anticalculi effect of apigenin with that of celery extract.Materials and Methods: Wistar albino rats were given ethylene glycol 0.75% (vol/vol) and ammonium chloride 2% (wt/vol) orally for 7 days in all groups to induce hyperoxaluria and Rats treated by Apigenin at doses 1.2, 2.4, and 4.8 mg/kg of rat body weight and celery extract at doses of 200, 400, and 600 mg/kg of rat body weight as anticalculi. Measurements of calcium levels in the kidneys and urine of rats was obtained using atomic absorption spectroscopy. Data obtained were statistically analyzed with the IBM SPSS by ANOVA Method version 21.0 probability value

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PMID: 

Antioxidants (Basel). 2019 Oct 25 ;8(11). Epub 2019 Oct 25. PMID: 31731465

Abstract Title: 

Gastro-Protective and Anti-Oxidant Potential ofandon Pyloric Ligation/Indomethacin-Induced Ulceration in Rats.

Abstract: 

Recently, an alternative disease treatment approach is the research of medicaments from traditional medicine. Plants with anti-oxidant capabilities are used as herbal treatments for ulcer diseases. Medicinal/herbal extracts containing phytoconstituents have significant anti-ulcer activities in in vivo experiments on animal models, compared to reference drugs. The current study aims to inspect gastro-protective as well as in vitro and in vivo anti-oxidant potential ofandextracts on pyloric-ligation/indomethacin-induced gastric-ulceration in rats. Rats were divided into six groups: normal control, gastric ulcer control, two standard pretreatment groups receiving omeprazole and misoprostol, and two test pretreatment groups receivingand. Pretreatments were administrated orally for 14 days. On the 15th day, animals, excluding the normal control group, were exposed to pyloric-ligation followed by indomethacin injection. After four hours, the rat's stomachs were removed and gastric juice and blood samples were collected. Pyloric-ligation/indomethacin administration caused considerable elevation in ulcer number, ulcer index, acid and pepsin productivity, aggressive factors, and gastric mucosal lipid-peroxide contents. Moreover, reduction in titratable acidity, gastric mucosal nitric-oxide, anti-oxidant contents, and protective factors accompanied gastric-ulceration. Additionally, elevation in pro-inflammatory cytokines content and reduction in cystathionine-β-synthase and heme-oxygenase-1 expression was witnessed. Omeprazole, misoprostol,andpretreatments fixed blood and tissue biomarkers, thereby protecting them from pyloric-ligation/indomethacin-induced gastric-ulceration in rats, which is hopeful for clinical examinations.

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PMID: 

Front Pharmacol. 2019 ;10:793. Epub 2019 Jul 12. PMID: 31354500

Abstract Title: 

Perspectives Regarding the Role of Biochanin A in Humans.

Abstract: 

Biochanin A (BCA) is an isoflavone mainly found in red clover with poor solubility and oral absorption that is known to have various effects, including anti-inflammatory, estrogen-like, and glucose and lipid metabolism modulatory activity, as well as cancer preventive, neuroprotective, and drug interaction effects. BCA is already commercially available and is among the main ingredients in many types of supplements used to alleviate postmenopausal symptoms in women. The activity of BCA has not been adequately evaluated in humans. However, the results of manyandstudies investigating the potential health benefits of BCA are available, and the complex mechanisms by which BCA modulates transcription, apoptosis, metabolism, and immune responses have been revealed. Many efforts have been exerted to improve the poor bioavailability of BCA, and very promising results have been reported. This review focuses on the major effects of BCA and its possible molecular targets, potential uses, and limitations in health maintenance and treatment.

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PMID: 

J Nat Med. 2020 Mar 19. Epub 2020 Mar 19. PMID: 32193805

Abstract Title: 

The effects of inhibiting the activation of hepatic stellate cells by lignan components from the fruits of Schisandra chinensis and the mechanism of schisanhenol.

Abstract: 

Liver fibrosis is a pathological manifestation induced by chronic liver injury and may cause cirrhosis and liver cancer with the chronic progression of fibrosis. During the onset and progression of liver fibrosis, the activation of hepatic stellate cells (HSCs) is the core mechanism for the secretion of many extracellular matrices to induce fibrosis. Lignans are reportedly the main effective components of Schisandra chinensis with good anti-fibrosis effects. In this study, we compared the inhibiting effects of the seven lignan components from S. chinensis on HSC activation. We found that the seven lignans inhibited the activation of human HSCs (LX-2) in various degrees. Among all lignans, schisanhenol showed the best effect in inhibiting the activation of LX-2 with a dose-effect relationship. Sal also inhibited the phosphorylations of Smad1, Smad2, Smad3, extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), p38, and nuclear transcription factor-κB (NF-κB), as well as downregulated Smad4. All these findings suggested that schisanhenol may ameliorate liver fibrosis by inhibiting the transforming growth factor β (TGF-β)/Smad and mitogen-activated protein kinase (MAPK) signaling pathways. Remarkably, schisanhenol may be a potential anti-liver fibrosis drug and warrants further research.

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PMID: 

Curr Pharm Biotechnol. 2020 Mar 20. Epub 2020 Mar 20. PMID: 32196447

Abstract Title: 

Apigenin alleviates renal fibroblast activation through AMPK and ERK signaling pathways in vitro.

Abstract: 

AIMS: The purpose of this study was to investigate the influences of apigenin on proliferation, differentiation and function of renal fibroblast after TGF-β1 stimulation and to uncover the underlying mechanisms.BACKGROUND: Renal fibrosis is a common pathway leading to the progression of chronic kidney disease. Activated fibroblasts contribute remarkably to the development of renal fibrosis. Although apigenin has been demonstrated to play a protective role from fibrotic diseases, its pharmacological effect on renal fibroblast activation remains largely unknown.OBJECTIVE: Here, we examined the functional role of apigenin in the activation of renal fibroblasts response to transforming growth factor (TGF)-β1 and its potential mechanisms.METHOD: Cultured renal fibroblasts (NRK-49F) were exposed to apigenin (1, 5, 10 and 20µM) followed by the stimulation of TGF-β1 (2 ng/mL) for 24 h. The markers of fibroblast activation were determined. In order to confirm the anti-fibrosis effect of apigenin, the expression of fibrosis-associated genes in renal fibroblasts was assessed.RESULT: As a consequence, apigenin alleviated fibroblast proliferation and fibroblast-myofibroblast differentiation induced by TGF-β1. Notably, apigenin significantly inhibited the fibrosis-associated genes expression in renal fibroblasts. Moreover, apigenin treatment significantly increased phosphorylation of AMP-activated protein kinase (AMPK). Apigenin treatment also obviously reduced TGF-β1 induced phosphorylation of ERK1/2 but not Smad2/3, p38 and JNK MAPK in renal fibroblasts.CONCLUSION: In a summary, these results indicate that apigenin inhibits renal fibroblast proliferation, differentiation and function by AMPK activation and reduced of ERK1/2 phosphorylation, suggesting it could be an attractive therapeutic potential for the treatment of renal fibrosis.

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PMID: 

Kidney Res Clin Pract. 2014 Dec ;33(4):181-6. Epub 2014 Nov 12. PMID: 26885474

Abstract Title: 

Mechanisms of phytoestrogen biochanin A-induced vasorelaxation in renovascular hypertensive rats.

Abstract: 

BACKGROUND: The plant-derived estrogen biochanin A is known to cause vasodilation, but its mechanism of action in hypertension remains unclear. This study was undertaken to investigate the effects and mechanisms of biochanin A on the thoracic aorta in two-kidney, one clip (2K1C) renovascular hypertensive rats.METHODS: Hypertension was induced by clipping the left renal artery, and control age-matched rats were sham treated. Thoracic aortae were mounted in tissue baths to measure isometric tension.RESULTS: Biochanin A caused concentration-dependent relaxation in aortic rings from 2K1C hypertensive and sham-treated rats, which was greater in 2K1C rats than in sham rats. Biochanin A-induced relaxation was significantly attenuated by removing the endothelium in aortic rings from 2K1C rats, but not in sham rats. N (ω)-Nitro-l-arginine methyl ester, a nitric oxide synthase inhibitor, or indomethacin, a cyclooxygenase inhibitor, did not affect the biochanin A-induced relaxation in aortic rings from 2K1C and sham rats. By contrast, treatment with glibenclamide, a selective inhibitor of adenosine triphosphate-sensitive K(+) channels, or tetraethylammonium, an inhibitor of Ca(2+)-activated K(+) channels, significantly reduced biochanin A-induced relaxation in aortic rings from both groups. However, 4-aminopyridine, a selective inhibitor of voltage-dependent K(+) channels, inhibited the relaxation induced bybiochanin A in 2K1C rats, whereas no significant differences were observed in sham rats.CONCLUSION: These results suggest that the enhanced relaxation caused by biochanin A in aortic rings from hypertensive rats is endothelium dependent. Vascular smooth muscle K(+) channels may be involved in biochanin A-induced relaxation in aortae from hypertensive and normotensive rats. In addition, an endothelium-derived activation of voltage-dependent K(+) channels contributes, at least in part, to the relaxant effect of biochanin A in renovascular hypertension.

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PMID: 

Life Sci. 2018 May 15 ;201:9-16. Epub 2018 Mar 19. PMID: 29567078

Abstract Title: 

Beneficial role of biochanin A on cutaneous and renal tissues of ovariectomized rats treated with anastrozole.

Abstract: 

AIMS: This study was designed to assess the beneficial role of biochanin A (BCA) in the protection of the cutaneous and renal tissues of ovariectomized rats, even in those treated with anastrozole (ANA).MATERIALS AND METHODS: For this purpose, 60 adult female Wistar rats were allocated into 6 equal groups. Rats in group I (sham) underwent a sham operation and received distilled water orally. In groups II and III, OVX rats received either distilled water orally or DMSO intraperitoneally, respectively. In groups IV and V, OVX rats were either treated orally with 0.5 mg ANA/kg.b.wt. or administered 5 mg of BCA/kg.b.wt. intraperitoneally, respectively. In group VI (OVX-ANA-BCA), OVX rats were co-treated with BCA and ANA. All treatments were given daily for 20 weeks.KEY FINDINGS: The IP administration of BCA significantly decreased serum levels of urea, creatinine, uric acid and MDA and significantly increased serum CAT, GSH and TAC and cutaneous IL-4 and GATA3 concentrations in the fifth and sixth groups compared to OVX-DMSO and OVX-ANA groups, respectively. Additionally, it induced down-regulation of renal TNF-α and iNOS expression as well as up-regulation of cutaneous TGF-β expression. Furthermore, BCA ameliorated to variable degrees histological changes of renal and cutaneous tissue related to ovariectomy and/or ANA treatment.SIGNIFICANCE: These data suggest that BCA might be a useful alternative estrogen therapy for the management of renal and cutaneous changes observed in postmenopausal women, even in those treated with ANA.

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PMID: 

J Ethnopharmacol. 2019 Dec 5 ;245:112173. Epub 2019 Aug 21. PMID: 31445129

Abstract Title: 

The role and mechanism of Asian medicinal plants in treating skin pigmentary disorders.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Chloasma, senile plaques, vitiligo and other pigmentary disorders seriously affect patients' appearance and life quality. Medicinal plant is the product of long-term medical practice worldwide, with the advantages of outstanding curative properties and less side effects. Recently, research were made to explore the value of medicinal plants in the treatment of pigmentary disorders, and remarkable results were achieved.AIM OF THE REVIEW: This review outlines the current understanding of the role and potential mechanisms of medicinal plants (including active ingredients, extracts and prescriptions) in pigmentary disorders, especially Chinese medicinal plants, provides the preclinical evidence for the clinical benefits. This study hopes to provide comprehensive information and reliable basis for exploring new therapeutic strategies of plant drugs in the treatment of skin pigmented diseases.METHODS: The literature information was obtained from the scientific databases (up to Oct, 2017), mainly from the PubMed, Web of Science and CNKI databases, and was to identify the experimental studies on the regulating melanogenesis role of the active agents from herbal medicine and the involved mechanisms. The search keywords for such work included:"pigmentary"or"pigmentation","melanogenesis", and"traditional Chinese medicine"or"Chinese herbal medicine","herb","medicinal plant".RESULTS: We summarized the function of medicinal plants involved in melanogenesis, especially Chinese medicine. It was reported that the active ingredients, extracts, or prescriptions of medicinal plants can regulate the expression of genes related to melanogenesis by affecting the signaling pathways such as MAPK and PKA, thereby regulating pigment synthesis. Some of them can promote melanogenesis (such as isoliquiritigenin, geniposide; Cornus officinalis Siebold&Zucc., Eclipta prostrata (L.) L.; the Bairesi complex prescription, etc.). While others have the opposite effect (such as biochanin A, Gomisin N; Panax ginseng C.A. Meyer, Nardostachys chinensis Bat.; Sanbaitang, etc.).CONCLUSION: Asian medicinal plants, especially their active ingredients, have multilevel effects on melanogenesis by regulating melanogenesis-related genes or signaling pathways. They are of great clinical value for the treatment of skin pigmentary disorders. However, the experimental effect, safety, and functional mechanism of the medicinal plants require further determination before studying their clinical efficacy.

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PMID: 

Food Chem Toxicol. 2020 Jan ;135:110924. Epub 2019 Oct 28. PMID: 31672514

Abstract Title: 

Quercetin as a Lyn kinase inhibitor inhibits IgE-mediated allergic conjunctivitis.

Abstract: 

BACKGROUND: Allergic conjunctivitis (AC) resulting from conjunctival reactive inflammation is a common ocular surface disease. Quercetin is known for its anti-allergic properties but its effects on conjunctivitis are less well understood.PURPOSE: In this study, we evaluated the anti-allergic effects of quercetin in animal models of conjunctivitis, and explored its molecular mechanism(s) of action in cultured human mast cells (MCs).KEY RESULTS: Quercetin inhibited the ovalbumin (OVA) induced expression of IgE, HA, IL-4, TNF-α and substance-P in the peripheral blood of AC mouse models. Quercetin also attenuated OVA induced MC degranulation, eosinophil number, substance P concentrations, and mRNA IL-4/TNF-α expression in the conjunctival tissue of AC models. In vitro analysis showed that quercetin reduced DNP-HSA/IgE induced calcium (Ca2+) influx, and suppressed degranulation and chemokine release in LAD2 cells (human primary mast cell). Quercetin also inhibited DNP-HSA/IgE induced Lyn/PLCγ/IP3R-Ca2+ activation, Lyn/ERK1/2 signaling, and Lyn/NF-κB activation in LAD2 cells, all of which promote inflammation. When added alone, quercetin had no effect on PLCγ1 phosphorylation or expression, but potently inhibited Lyn and phosphorylation-Lyn. Quercetin (200 μM) and Lyn inhibitors (Bafetinib, 10 μM) inhibit the activity of Lyn kinase, and quercetin can reduce the activation of Lyn kinase by Lyn agonist (Tolimidone, 10 μM). These data can be preliminarily determined that quercetin can inhibit allergic conjunctivitis as a Lyn kinase inhibitor.CONCLUSIONS AND IMPLICATIONS: This study illustrated the use of quercetin for the treatment of allergic conjunctivitis, which might act through its ability to inhibit Lyn/PLCγ/IP3R-Ca, Lyn/ERK1/2, and Lyn/NF-κB signaling. The inhibition of Lyn likely represents a major mechanism by which quercetin dampens the inflammatory response in AC disease models.

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