Clinical efficacy; Drug interaction; Flavonoids; Pharmacology; Saponins; Toxicology; Drugs, Chinese Herbal; Phytochemicals; Plant Extracts; Humans; Male; Ethnopharmacology; Flavonoids/pharmacology; Phytochemicals/pharmacology; Plant Extracts/pharmacology; Meta-Analysis as Topic; Systematic Reviews as Topic; Drugs, Chinese Herbal/pharmacology; Saponins/pharmacology; Molecular Medicine; Pharmaceutical Science; Drug Discovery; Complementary and Alternative Medicine
Abstract :
[en] [en] BACKGROUND: Flavonoids and saponins are important bioactive compounds that have attracted wide research interests. This review aims to summarise the state of the art of the pharmacology, toxicology and clinical efficacy of these compounds.
METHODS: Data were retrieved from PubMed, Cochrane Library, Web of Science, Proquest, CNKI, Chongqing VIP, Wanfang, NPASS and HIT 2.0 databases. Meta-analysis and systematic reviews were evaluated following the PRISMA guideline. Statistical analyses were conducted using SPSS23.0.
RESULTS: Rising research trends on flavonoids and saponins were observed since the 1990s and the 2000s, respectively. Studies on pharmacological targets and activities of flavonoids and saponins represent an important area of research advances over the past decade, and these important resources have been documented in open-access specialised databases and can be retrieved with ease. The rising research on flavonoids and saponins can be attributed, at least in part, to their links with some highly investigated fields of research, e.g., oxidative stress, inflammation and cancer; i.e., 6.88% and 3.03% of publications on oxidative stress cited by PubMed in 1990 - 2021 involved flavonoids and saponins, respectively, significantly higher than the percentage involving alkaloids (1.88%). The effects of flavonoids concern chronic venous insufficiency, cervical lesions, diabetes, rhinitis, dermatopathy, prostatitis, menopausal symptoms, angina pectoris, male pattern hair loss, lymphocytic leukaemia, gastrointestinal diseases and traumatic cerebral infarction, etc, while those of saponins may have impact on venous oedema in chronic deep vein incompetence, erectile dysfunction, acute impact injuries and systemic lupus erythematosus, etc. The volume of in vitro research appears way higher than in vivo and clinical studies, with only 10 meta-analyses and systematic reviews (involving 290 interventional and observational studies), and 36 clinical studies on flavonoids and saponins. Data are sorely needed on pharmacokinetics, in vitro pan-assay interferences, purity of tested compounds, interactions in complex herbal extracts, real impact of anti-oxidative strategies, and mid- and long-term toxicities. To fill these important gaps, further investigations are warranted. On the other hand, drug interactions may cause adverse effects but might also be useful for synergism, with the goals of enhancing effects or of detoxifying. Furthermore, the interactions between phytochemicals and the intestinal microbiota are worth investigating as the field may present a promising potential for novel drug development.
Disciplines :
Pharmacy, pharmacology & toxicology Alternative medicine Food science
Author, co-author :
Wang, Xuanbin ; Laboratory of Chinese Herbal Pharmacology, Department of Pharmacy, Renmin Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Biomedical Research Institute, School of Pharmaceutical Sciences and Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, South Renmin Road, Shiyan, 442000, China.. Electronic address: wangxb@hbmu.edu.cn
Ma, Yan; Molecular Research in Traditional Chinese Medicine, Division of Comparative Immunology and Oncology, Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Vienna General Hospital, Medical University of Vienna
Xu, Qihe; Renal Sciences and Integrative Chinese Medicine Laboratory, Department of Inflammation Biology, School of Immunology & Microbial Sciences, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom
Shikov, Alexander N ; Saint-Petersburg State Chemical Pharmaceutical University, Prof. Popov, 14, Saint-Petersburg, 197376, Russia
Pozharitskaya, Olga N; Murmansk Marine Biological Institute of the Russian Academy of Sciences, Vladimirskaya, 17, Murmansk, 183010, Russia
Flisyuk, Elena V; Saint-Petersburg State Chemical Pharmaceutical University, Prof. Popov, 14, Saint-Petersburg, 197376, Russia
Liu, Meifeng; Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China
Li, Hongliang ; Laboratory of Chinese Herbal Pharmacology, Department of Pharmacy, Renmin Hospital, Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Biomedical Research Institute, School of Pharmaceutical Sciences and Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, South Renmin Road, Shiyan, 442000, China
Vargas-Murga, Liliana ; BIOTHANI, Can Lleganya, 17451 Sant Feliu de Buixalleu, Catalonia, Spain, Department of Chemical and Agricultural Engineering and Agrifood Technology, University of Girona (UdG), 17003 Girona, Catalonia, Spain
R550 - Institut des Sciences et Technologies de la Santé
Funding text :
The study was financially supported by the National Natural Science Foundation of China ( 81874356 ; 82274155 ); the Open Project of Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine) ( WDCM2018002 ; WDCM201917 ; WDCM201918 ); the Chinese Medicine Project of Health Commission of Hubei Province ( ZY2021Z010 ; WJ2021M055 ); the Advantages Discipline Group (Medicine) Project in Higher Education of Hubei Province ( 2022XKQY3 ); the Commission de la Coopération au Développement of the Belgian Académie de Recherche et d'Enseignement Supérieur (ARES-CCD), through the PRD project PhytoKat. The funders played no role in the design of this study or in the collection, analysis, and interpretation of data and the writing of the manuscript, which are completely the responsibilities of the authors.
Abere, T.A., Okoto, P.E., Agoreyo, F.O., Antidiarrhoea and toxicological evaluation of the leaf extract of Dissotis rotundifolia Triana (Melastomataceae). BMC Compl. Altern. Med., 10, 2010, 71, 10.1186/1472-6882-10-71 Doi:.
Adeoye, R.I., Joel, E.B., Igunnu, A., Arise, R.O., Malomo, S.O., A review of some common African spices with antihypertensive potential. J. Food Biochem., 46, 2022, e14003, 10.1111/jfbc.14003 Doi:.
Agosta, C., Atlante, M., Benvenuti, C., Randomized controlled study on clinical efficacy of isoflavones plus Lactobacillus sporogenes, associated or not with a natural anxiolytic agent in menopause. Minerva Ginecol. 63 (2011), 11–17 Doi:.
Ahn, W.S., Yoo, J., Huh, S.W., Kim, C.K., Lee, J.M., Namkoong, S.E., et al. Protective effects of green tea extracts (polyphenon E and EGCG) on human cervical lesions. Eur. J. Cancer Prev. 12 (2003), 383–390, 10.1097/00008469-200310000-00007 Doi:.
Baell, J.B., Feeling Nature's PAINS: Natural Products, Natural Product Drugs, and Pan Assay Interference Compounds (PAINS). J. Nat. Prod. 79 (2016), 616–628, 10.1021/acs.jnatprod.5b00947 Doi:.
Belaya, N.y., Belyi, A., Tikhonova, G., Udalov, Y., Andriyenko, G., Synergistic effect of binary quercetin-monosaccharide mixtures in the reaction with free radicals. Izvestiya Vysshikh Uchebnykh Zavedenii Khimiya Khimicheskaya Tekhnologiya 62 (2019), 38–42, 10.6060/ivkkt.20196202.5822 Doi:.
Berkers, G., van der Meer, R., van Mourik, P., Vonk, A.M., Kruisselbrink, E., Suen, S.W., et al. Clinical effects of the three CFTR potentiator treatments curcumin, genistein and ivacaftor in patients with the CFTR-S1251N gating mutation. J. Cyst. Fibros. 19 (2020), 955–961, 10.1016/j.jcf.2020.04.014 Doi:.
Bisson, J., McAlpine, J.B., Friesen, J.B., Chen, S.N., Graham, J., Pauli, G.F., Can invalid Bioactives undermine natural product-based drug discovery?. J. Med. Chem. 59 (2016), 1671–1690, 10.1021/acs.jmedchem.5b01009 Doi:.
Cai, T., Mazzoli, S., Bechi, A., Addonisio, P., Mondaini, N., Pagliai, R.C., et al. Serenoa repens associated with Urtica dioica (ProstaMEV) and curcumin and quercitin (FlogMEV) extracts are able to improve the efficacy of prulifloxacin in bacterial prostatitis patients: results from a prospective randomised study. Int. J. Antimicrob. Agents 33 (2009), 549–553, 10.1016/j.ijantimicag.2008.11.012 Doi:.
Cao, W., Liu, W., Wu, T., Zhong, D., Liu, G., Dengzhanhua preparations for acute cerebral infarction. The Cochrane database of systematic reviews Issue 4. Art. CD005568, CD005568, 2008, 10.1002/14651858.CD005568.pub2 Doi:.
Capuzzi, S.J., Muratov, E.N., Tropsha, A., Phantom PAINS: Problems with the Utility of Alerts for Pan-Assay INterference CompoundS. J. Chem. Inf. Model. 57 (2017), 417–427, 10.1021/acs.jcim.6b00465 Doi:.
Cardoso, C.R., de Syllos Cólus, I.M., Bernardi, C.C., Sannomiya, M., Vilegas, W., Varanda, E.A., Mutagenic activity promoted by amentoflavone and methanolic extract of Byrsonima crassa Niedenzu. Toxicology 225 (2006), 55–63, 10.1016/j.tox.2006.05.003 Doi:.
Carpentier, P., van Bellen, B., Karetova, D., Hanafiah, H., Enriquez-Vega, E., Kirienko, A., et al. Clinical efficacy and safety of a new 1000-mg suspension versus twice-daily 500-mg tablets of MPFF in patients with symptomatic chronic venous disorders: a randomized controlled trial. Int. Angiol. 36 (2017), 402–409, 10.23736/s0392-9590.17.03801-9 Doi:.
Cassidy, A., Minihane, A.M., The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids. Am. J. Clin. Nutr. 105 (2017), 10–22, 10.3945/ajcn.116.136051 Doi:.
Cesarone, M.R., Belcaro, G., Ippolito, E., Pellegrini, L., Ledda, A., Luzzi, R., et al. Clinical improvement in chronic venous insufficiency signs and symptoms with Venoruton® (HR): an 8-month, open-registry, cost-efficacy study. Panminerva Med. 52 (2010), 43–48 Doi:.
Cesarone, M.R., Belcaro, G., Rohdewald, P., Pellegrini, L., Ledda, A., Vinciguerra, G., et al. Comparison of Pycnogenol and Daflon in treating chronic venous insufficiency: a prospective, controlled study. Clin. Appl. Thromb. Hemost. 12 (2006), 205–212, 10.1177/107602960601200209 Doi:.
Cesarone, M.R., Belcaro, G., Rohdewald, P., Pellegrini, L., Ledda, A., Vinciguerra, G., et al. Rapid relief of signs/symptoms in chronic venous microangiopathy with pycnogenol: a prospective, controlled study. Angiology 57 (2006), 569–576, 10.1177/0003319706291392 Doi:.
Cesarone, M.R., Belcaro, G., Rohdewald, P., Pellegrini, L., Ledda, A., Vinciguerra, G., et al. Improvement of diabetic microangiopathy with pycnogenol: a prospective, controlled study. Angiology 57 (2006), 431–436, 10.1177/0003319706290318 Doi:.
Cesarone, M.R., Belcaro, G., Rohdewald, P., Pellegrini, L., Ledda, A., Vinciguerra, G., et al. Improvement of signs and symptoms of chronic venous insufficiency and microangiopathy with Pycnogenol: a prospective, controlled study. Phytomedicine 17 (2010), 835–839, 10.1016/j.phymed.2010.04.009 Doi:.
Chai, C.L., Mátyus, P., One size does not fit all: challenging some dogmas and taboos in drug discovery. Future Med. Chem. 8 (2016), 29–38, 10.4155/fmc.15.167 Doi:.
Chan, L.Y., Chiu, P.Y., Lau, T.K., Embryotoxicity study of ginsenoside Rc and Re in in vitro rat whole embryo culture. Reprod. Toxicol. 19 (2004), 131–134, 10.1016/j.reprotox.2004.06.001 Doi:.
Chan, Y.T., Cheung, F., Zhang, C., Fu, B., Tan, H.Y., Norimoto, H., et al. Ancient chinese medicine herbal formula huanglian jiedu decoction as a neoadjuvant treatment of chemotherapy by improving diarrhea and tumor response. Front. Pharmacol., 11, 2020, 252, 10.3389/fphar.2020.00252 Doi:.
Chen, J., Li, G., Sun, C., Peng, F., Yu, L., Chen, Y., et al. Chemistry, pharmacokinetics, pharmacological activities, and toxicity of Quercitrin. Phytother. Res. 36 (2022), 1545–1575, 10.1002/ptr.7397 Doi:.
Chen, W., Wang, S., Wu, Y., Shen, X., Xu, S., Guo, Z., et al. The Physiologic Activity and Mechanism of Quercetin-Like Natural Plant Flavonoids. Curr. Pharm. Biotechnol. 21 (2020), 654–658, 10.2174/1389201021666200212093130 Doi:.
Chen, X., Zhou, M., Li, Q., Yang, J., Zhang, Y., Zhang, D., et al. Sanchi for acute ischaemic stroke. Cochrane Database Systematic Rev.(4), 2008, CD006305, 10.1002/14651858.CD006305.pub2 IssueArt. No.Doi:.
Chen, Y., Guo, Q., Zhu, Z., Zhang, L., Changes in bioactive components related to the harvest time from the spicas of Prunella vulgaris. Pharm. Biol. 50 (2012), 1118–1122, 10.3109/13880209.2012.658477 Doi:.
Choi, H.K., Seong, D.H., Rha, K.H., Clinical efficacy of Korean red ginseng for erectile dysfunction. Int. J. Impot. Res. 7 (1995), 181–186 Doi:.
Choi, S., Youn, J., Kim, K., Joo da, H., Shin, S., Lee, J., et al. N. Apigenin inhibits UVA-induced cytotoxicity in vitro and prevents signs of skin aging in vivo. Int. J. Mol. Med. 38 (2016), 627–634, 10.3892/ijmm.2016.2626 Doi:.
Chou, T.C., Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol. Rev. 58 (2006), 621–681, 10.1124/pr.58.3.10 Doi:.
Collett, M.G., Thompson, K.G., Christie, R.J., Photosensitisation, crystal-associated cholangiohepatopathy, and acute renal tubular necrosis in calves following ingestion of Phytolacca octandra (inkweed). N. Z. Vet. J. 59 (2011), 147–152, 10.1080/00480169.2011.567966 Doi:.
Daley, S.-k., Cordell, G.A., Alkaloids in Contemporary Drug Discovery To Meet Global Disease Needs. Molecules, 26, 2021, 3800 Doi:.
De Lucca, A.J., Bland, J.M., Boue, S., Vigo, C.B., Cleveland, T.E., Walsh, T.J., Synergism of CAY-1 with amphotericin B and itraconazole. Chemotherapy 52 (2006), 285–287, 10.1159/000095959 Doi:.
de Ruijter, J., Valstar, M.J., Narajczyk, M., Wegrzyn, G., Kulik, W., Ijlst, L., et al. Genistein in Sanfilippo disease: a randomized controlled crossover trial. Ann. Neurol. 71 (2012), 110–120, 10.1002/ana.22643 Doi:.
Dewick, P.M., Medicinal Natural Products, 3rd, 2009, John Wiley& Sons Ltd, Chichester, West Sussex, England, 336.
Di, Q.S., Xu, T., Song, Y., Zuo, Z.G., Cao, F.J., Yu, X.J., et al. High C-reactive protein to albumin ratio predicts inferior clinical outcomes in extranodal natural Killer T-Cell Lymphoma. Dose-response: publ. Int. Hormesis Soc., 18, 2020, 1559325820917824, 10.1177/1559325820917824 Doi:.
Diehm, C., Vollbrecht, D., Amendt, K., Comberg, H.U., Medical edema protection–clinical benefit in patients with chronic deep vein incompetence. A placebo controlled double blind study. VASA. Zeitschrift fur Gefasskrankheiten 21 (1992), 188–192 Doi:.
Ding, Y., Liu, Y., Li, H., Li, Y., Li, M., Liu, M., et al. Chinese medicines for preventing and treating radiation-induced pulmonary injury: still a long way to go. Front. Pharmacol., 10, 2019, 927, 10.3389/fphar.2019.00927 Doi:.
Dobrzynska, M., Napierala, M., Florek, E., Flavonoid nanoparticles: a promising approach for cancer therapy. Biomolecules, 10, 2020, 10.3390/biom10091268 Doi:.
Eid, S.Y., El-Readi, M.Z., Wink, M., Digitonin synergistically enhances the cytotoxicity of plant secondary metabolites in cancer cells. Phytomedicine 19 (2012), 1307–1314, 10.1016/j.phymed.2012.09.002 Doi:.
Ellwood, L., Torun, G., Bahar, Z., Fernandez, R., Effectiveness of flavonoid rich fruits for hypertension in adults: a systematic review protocol. JBI Database Syst. Rev. Implement. Rep. 16 (2018), 2103–2108, 10.11124/JBISRIR-2017-003804 Doi:.
Filippini, T., Malavolti, M., Borrelli, F., Izzo, A.A., Fairweather-Tait, S.J., Horneber, M., et al., 2020. Green tea (Camellia sinensis) for the prevention of cancer. Doi: 10.1002/14651858.CD005004.pub3.
Fuloria, S., Yusri, M.A.A., Sekar, M., Gan, S.H., Rani, N., Lum, P.T., et al. Genistein: a potential natural lead molecule for new drug design and development for treating memory impairment. Molecules, 27, 2022, 10.3390/molecules27010265 Doi:.
Furumura, M., Sato, N., Kusaba, N., Takagaki, K., Nakayama, J., Oral administration of French maritime pine bark extract (Flavangenol(®)) improves clinical symptoms in photoaged facial skin. Clin. Interv. Aging 7 (2012), 275–286, 10.2147/cia.s33165 Doi:.
Gallelli, G., Cione, E., Serra, R., Leo, A., Citraro, R., Matricardi, P., et al. Nano-hydrogel embedded with quercetin and oleic acid as a new formulation in the treatment of diabetic foot ulcer: A pilot study. Int. Wound J. 17 (2020), 485–490, 10.1111/iwj.13299 Doi:.
Gao, Y.L., Liu, Z.F., Li, C.M., Shen, J.Y., Yin, H.X., Li, G.S., Subchronic toxicity studies with ginsenoside compound K delivered to dogs via intravenous administration. Food Chem. Toxicol. 49 (2011), 1857–1862, 10.1016/j.fct.2011.05.003 Doi:.
Gevrenova, R., Zaharieva, M.M., Kroumov, A.D., Voutquenne-Nazabadioko, L., Zheleva-Dimitrova, D., Balabanova, V., et al. Gypsophila saponins enhance the cytotoxicity of etoposide in HD-MY-Z lymphoma cells. Food Chem. Toxicol., 133, 2019, 110777, 10.1016/j.fct.2019.110777 Doi:.
Ghosh, A., Rust, S., Langford-Smith, K., Weisberg, D., Canal, M., Breen, C., et al. High dose genistein in Sanfilippo syndrome: a randomised controlled trial. J. Inherit. Metab. Dis. 44 (2021), 1248–1262, 10.1002/jimd.12407 Doi:.
Gou, S.H., He, M., Li, B.B., Zhu, N.Y., Ni, J.M., Hepatoprotective effect of total flavonoids from Glycyrrhiza uralensis Fisch in liver injury mice. Nat. Prod. Res. 35 (2021), 6083–6087, 10.1080/14786419.2020.1824223 Doi:.
Grundy, D., Signalling the state of the digestive tract. Auton. Neurosci. 125 (2006), 76–80, 10.1016/j.autneu.2006.01.009 Doi:.
Gupta, J., Ahuja, A., Gupta, R., Green approaches for cancers management: an effective tool for health care. Anticancer Agents Med. Chem. 22 (2022), 101–114, 10.2174/1871520621666210119091826 Doi:.
Hajimehdipoor, H., Shahrestani, R., Shekarchi, M., Investigating the synergistic antioxidant effects of some flavonoid and phenolic compounds. Res. J. Pharmacognosy 1 (2014), 35–40 Doi:.
Hamed, K.A., El-Fiky, S.A., Gawish, A.M., Khalil, W.K.B., Mohamed, H.R.H., Alleviation of nicotine-induced reproductive disorder, clastogenicity, and histopathological alterations by fenugreek saponin bulk and nanoparticles in male rats. Environ. Sci. Pollut. Res. Int., 2022, 10.1007/s11356-022-19123-z Doi:.
Hanahan, D., Weinberg, R.A., The hallmarks of cancer. Cell 100 (2000), 57–70, 10.1016/s0092-8674(00)81683-9 Doi:.
He, Y., Ci, X., Xie, Y., Yi, X., Zeng, Y., Li, Y., et al. Potential detoxification effect of active ingredients in liquorice by upregulating efflux transporter. Phytomedicine 56 (2019), 175–182, 10.1016/j.phymed.2018.10.033 Doi:.
He, Y., Hu, Z., Li, A., Zhu, Z., Yang, N., Ying, Z., et al. Recent advances in biotransformation of saponins. Molecules, 24, 2019, 10.3390/molecules24132365 Doi:.
Heimfarth, L., Nascimento, L.D.S., Amazonas da Silva, M.J., Lucca Junior, W., Lima, E.S., Quintans-Junior, L.J., et al. Neuroprotective and anti-inflammatory effect of pectolinarigenin, a flavonoid from Amazonian Aegiphila integrifolia (Jacq.), against lipopolysaccharide-induced inflammation in astrocytes via NFkappaB and MAPK pathways. Food Chem. Toxicol., 157, 2021, 112538, 10.1016/j.fct.2021.112538 Doi:.
Herrmann, F., Wink, M., Synergistic interactions of saponins and monoterpenes in HeLa cells, Cos7 cells and in erythrocytes. Phytomedicine 18 (2011), 1191–1196, 10.1016/j.phymed.2011.08.070 Doi:.
Hidalgo, M., Sánchez-Moreno, C., de Pascual-Teresa, S., Flavonoid-flavonoid interaction and its effect on their antioxidant activity. Food Chem. 121:691-696 (2010), 691–696, 10.1016/j.foodchem.2009.12.097 Doi:.
HMPC (Committee on Herbal Medicinal Products). Assessment report on Panax ginseng C.A, 2014, Meyer, radix. European Medicines Agency, 124 https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-panax-ginseng-ca-meyer-radix_en.pdf.
Homhual, S., Bunyapraphatsara, N., Kondratyuk, T., Herunsalee, A., Chaukul, W., Pezzuto, J.M., et al. Bioactive dammarane triterpenes from the mangrove plant Bruguiera gymnorrhiza. J. Nat. Prod. 69 (2006), 421–424, 10.1021/np058112x Doi:.
Hosseinzadeh, E., Hassanzadeh, A., Marofi, F., Alivand, M.R., Solali, S., Flavonoid-based cancer therapy: an updated review. Anticancer Agents Med. Chem. 20 (2020), 1398–1414, 10.2174/1871520620666200423071759 Doi:.
Hussein, R.M., Mohamed, W.R., Omar, H.A., A neuroprotective role of kaempferol against chlorpyrifos-induced oxidative stress and memory deficits in rats via GSK3beta-Nrf2 signaling pathway. Pestic. Biochem. Physiol. 152 (2018), 29–37, 10.1016/j.pestbp.2018.08.008 Doi:.
Imran, M., Rauf, A., Abu-Izneid, T., Nadeem, M., Shariati, M.A., Khan, I.A., et al. Luteolin, a flavonoid, as an anticancer agent: a review. Biomed. Pharmacother., 112, 2019, 108612, 10.1016/j.biopha.2019.108612 Doi:.
Kandhare, A.D., Bodhankar, S.L., Mohan, V., Thakurdesai, P.A., Acute and repeated doses (28 days) oral toxicity study of Vicenin-1, a flavonoid glycoside isolated from fenugreek seeds in laboratory mice. Regul. Toxicol. Pharmacol. 81 (2016), 522–531, 10.1016/j.yrtph.2016.10.013 Doi:.
Kang, K.B., Ryu, J., Cho, Y., Choi, S.Z., Son, M., Sung, S.H., Combined application of UHPLC-QTOF/MS, HPLC-ELSD and (1) H-NMR spectroscopy for quality assessment of DA-9801, A Standardised dioscorea extract. Phytochem. Anal. 28 (2017), 185–194, 10.1002/pca.2659 Doi:.
Kang, S., Kim, J.E., Song, N.R., Jung, S.K., Lee, M.H., Park, J.S., et al. The ginsenoside 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol induces autophagy and apoptosis in human melanoma via AMPK/JNK phosphorylation. PLoS One, 9, 2014, e104305, 10.1371/journal.pone.0104305 Doi:.
Khan, A., Ikram, M., Hahm, J.R., Kim, M.O., Antioxidant and anti-inflammatory effects of citrus flavonoid Hesperetin: special focus on neurological disorders. Antioxidants (Basel), 2020, 9, 10.3390/antiox9070609 Doi:.
Khanduja, K.L., Verma, A., Bhardwaj, A., Impairment of human sperm motility and viability by quercetin is independent of lipid peroxidation. Andrologia 33 (2001), 277–281, 10.1046/j.1439-0272.2001.00432.x Doi:.
Kiatwuthinon, P., Narkthong, T., Ngaokrajang, U., Kumkate, S., Janvilisri, T., Baicalein inhibits metastatic phenotypes in nasopharyngeal carcinoma cells via a focal adhesion protein Integrin beta8. Pharmaceuticals, 15, 2021, 10.3390/ph15010005 Doi:.
Kim, D.U., Chung, H.C., Kim, C., Hwang, J.K., Oral intake of Boesenbergia pandurata extract improves skin hydration, gloss, and wrinkling: A randomized, double-blind, and placebo-controlled study. J. Cosmet. Dermatol. 16 (2017), 512–519, 10.1111/jocd.12343 Doi:.
Kim, S.Y., Lee, H.N., Hong, S.J., Kang, H.J., Cho, J.Y., Kim, D., et al. Enhanced biotransformation of the minor ginsenosides in red ginseng extract by Penicillium decumbens β-glucosidase. Enzyme Microb. Technol., 153, 2022, 109941, 10.1016/j.enzmictec.2021.109941 Doi:.
Kirienko, A., Radak, D., Maggioli, A., Clinical efficacy of once-daily micronized purified flavonoid fraction 1000 mg tablet in patients with symptomatic chronic venous disease. Curr. Med. Res. Opin. 35 (2019), 553–557, 10.1080/03007995.2018.1499508 Doi:.
Kurin, E., Mučaji, P., Nagy, M., In vitro antioxidant activities of three red wine polyphenols and their mixtures: an interaction study. Molecules 17 (2012), 14336–14348, 10.3390/molecules171214336 Doi:.
Lan, Z., Hu, C., Huang, Y., Chen, L., Ma, C., Mei, Z., et al. Safety assessment of saponins extract in Dolichos falcatus Klein: subchronic study in Sprague-Dawley rats. J. Ethnopharmacol. 174 (2015), 230–237, 10.1016/j.jep.2015.08.016 Doi:.
Lee, C.C., Kim, J.H., Kim, J.S., Oh, Y.S., Han, S.M., Park, J.H.Y., et al. 5-(3′,4′-Dihydroxyphenyl-γ-valerolactone), a major microbial metabolite of proanthocyanidin, Attenuates THP-1 monocyte-endothelial adhesion. Int. J. Mol. Sci., 18, 2017, 10.3390/ijms18071363 Doi:.
Lee, C.F., Yang, J.S., Tsai, F.J., Chiang, N.N., Lu, C.C., Huang, Y.S., et al. Kaempferol induces ATM/p53-mediated death receptor and mitochondrial apoptosis in human umbilical vein endothelial cells. Int. J. Oncol. 48 (2016), 2007–2014, 10.3892/ijo.2016.3420 Doi:.
Lee, H.S., Cho, H.J., Kwon, G.T., Park, J.H.Y., Kaempferol Downregulates Insulin-like Growth Factor-I Receptor and ErbB3 Signaling in HT-29 Human colon cancer cells. J. Cancer Prevent. 19 (2014), 161–169, 10.15430/jcp.2014.19.3.161 Doi:.
Li, F., Zhang, J., Lin, M., Su, X., Li, C., Wang, H., et al. Anti-inflammatory terpenes from Schefflera rubriflora C. J. Tseng & G. Hoo with their TNF-α and IL-6 inhibitory activities. Phytochemistry 163 (2019), 23–32, 10.1016/j.phytochem.2019.03.021 Doi:.
Li, H., Wei, W., Xu, H., Drug discovery is an eternal challenge for the biomedical sciences. Acta Materia Medica, 1, 2022, 10.15212/amm-2022-1001 Doi:.
Li, N., Zhou, T., Wu, F., Wang, R., Zhao, Q., Zhang, J.Q., et al. Pharmacokinetic mechanisms underlying the detoxification effect of Glycyrrhizae Radix et Rhizoma (Gancao): drug metabolizing enzymes, transporters, and beyond. Expert. Opin. Drug Metab. Toxicol. 15 (2019), 167–177, 10.1080/17425255.2019.1563595 Doi:.
Li, X., Li, X., Lu, J., Huang, Y., Lv, L., Luan, Y., et al. Saikosaponins induced hepatotoxicity in mice via lipid metabolism dysregulation and oxidative stress: a proteomic study. BMC Compl. Altern. Med., 17, 2017, 219, 10.1186/s12906-017-1733-0 Doi:.
Li, Y., Wang, D., Liu, J., Li, Y., Chen, D., Zhou, L., et al. Baicalin attenuates YAP activity to suppress ovarian cancer Stemness. Onco Targets Ther. 13 (2020), 7151–7163, 10.2147/ott.S254607 Doi:.
Li, Y.Y., Lu, X.Y., Sun, J.L., Wang, Q.Q., Zhang, Y.D., Zhang, J.B., et al. Potential hepatic and renal toxicity induced by the biflavonoids from Ginkgo biloba. Chin. J. Nat. Med. 17 (2019), 672–681, 10.1016/s1875-5364(19)30081-0 Doi:.
Li, Z., Liu, T., Liao, J., Ai, N., Fan, X., Cheng, Y., Deciphering chemical interactions between Glycyrrhizae Radix and Coptidis Rhizoma by liquid chromatography with transformed multiple reaction monitoring mass spectrometry. J. Sep. Sci. 40 (2017), 1254–1265, 10.1002/jssc.201601054 Doi:.
Liang, J., Jin, W., Li, H., Liu, H., Huang, Y., Shan, X., et al. In Vivo Cardiotoxicity Induced by Sodium Aescinate in Zebrafish Larvae. Molecules, 21, 2016, 190, 10.3390/molecules21030190 Doi:.
Lim, H.M., Park, S.H., Regulation of reactive oxygen species by phytochemicals for the management of cancer and diabetes. Crit. Rev. Food Sci. Nutr., 2022, 1–26, 10.1080/10408398.2022.2025574 Doi:.
Lindsjö, J., Fahlman, Å., Törnqvist, E., Animal welfare from mouse To Moose–implementing the principles of the 3rs In wildlife research. J. Wildl. Dis. 52 (2016), S65–S77, 10.7589/52.2s.s65 Doi:.
Liu, J., Peter, K., Shi, D., Zhang, L., Dong, G., Zhang, D., et al. Traditional formula, modern application: chinese medicine formula sini tang improves early ventricular remodeling and cardiac function after myocardial infarction in rats. Evid. Based Compl. Alternat. Med., 2014, 2014, 141938, 10.1155/2014/141938 Doi:.
Liu, J.P., Lu, D., Nicholson, R.C., Li, P.Y., Wang, F., Toxicity of a novel anti-tumor agent 20(S)-ginsenoside Rg3: a 26-week intramuscular repeated administration study in Beagle dogs. Food Chem. Toxicol. 49 (2011), 1718–1727, 10.1016/j.fct.2011.04.017 Doi:.
Liu, K., Li, H., Duan, J., Chen, X., Yu, X., Wang, X., et al. Progress in clinical research on the integration of Chinese and Western medicines for treating primary liver cancer. J. Trad. Chin. Med. Sci. 8 (2021), 173–185, 10.1016/j.jtcms.2021.07.001 Doi:.
Liu, W., Deng, S., Zhou, D., Huang, Y., Li, C., Hao, L., et al. 3,4-seco-dammarane triterpenoid saponins with anti-inflammatory activity isolated from the leaves of Cyclocarya paliurus. J. Agric. Food Chem. 68 (2020), 2041–2053, 10.1021/acs.jafc.9b06898 Doi:.
Loing, E., Lachance, R., Ollier, V., Hocquaux, M., A new strategy to modulate alopecia using a combination of two specific and unique ingredients. J. Cosmetic Sci. 64 (2013), 45–58 Doi:.
Lu, D., Liu, J., Zhao, W., Li, P., Chronic toxicity of ginsenoside Re on sprague-dawley rats. J. Ethnopharmacol. 144 (2012), 656–663, 10.1016/j.jep.2012.10.007 Doi:.
Lu, T.M., Chiu, H.F., Shen, Y.C., Chung, C.C., Venkatakrishnan, K., Wang, C.K., Hypocholesterolemic efficacy of quercetin rich onion juice in healthy Mild hypercholesterolemic adults: a pilot study. Plant Foods Hum. Nutr. 70 (2015), 395–400, 10.1007/s11130-015-0507-4 Doi:.
Lubo, L., Sulin, N., Zhimei, D., Houfa, N., Clinical efficacy and CT perfusion of puerarin combined with naloxone in the treatment of traumatic cerebral infarction. Pak. J. Pharm. Sci. 33 (2020), 423–428 Doi:.
Luo, Z.K., Liu, Y., Li, H.M., A clinical efficacy and safety study on coronary heart disease and angina treatment with Puerarin Injection. Zhonghua Liu Xing Bing Xue Za Zhi 33 (2012), 614–616 Doi:.
Lv, X., Zhang, J.B., Wang, X.X., Hu, W.Z., Shi, Y.S., Liu, S.W., et al. Amentoflavone is a potent broad-spectrum inhibitor of human UDP-glucuronosyltransferases. Chem. Biol. Interact. 284 (2018), 48–55, 10.1016/j.cbi.2018.02.009 Doi:.
Mahmoud, T.N., El-Maadawy, W.H., Kandil, Z.A., Khalil, H., El-Fiky, N.M., El Alfy, T., Canna x generalis L.H. Bailey rhizome extract ameliorates dextran sulfate sodium-induced colitis via modulating intestinal mucosal dysfunction, oxidative stress, inflammation, and TLR4/NF-B and NLRP3 inflammasome pathways. J. Ethnopharmacol., 269, 2021, 113670, 10.1016/j.jep.2020.113670 Doi:.
Martinez-Zapata, M.J., Vernooij, R.W.M., Simancas-Racines, D., Uriona Tuma, S.M., Stein, A., Moreno Carriles, R.M.M., et al. Phlebotonics for venous insufficiency. Cochrane Database Systematic Rev. Issue 11. Art., 2020, CD003229, 10.1002/14651858.CD003229.pub4 Doi:.
Memariani, Z., Abbas, S.Q., Ul Hassan, S.S., Ahmadi, A., Chabra, A., Naringin and naringenin as anticancer agents and adjuvants in cancer combination therapy: Efficacy and molecular mechanisms of action, a comprehensive narrative review. Pharmacol. Res., 171, 2021, 105264, 10.1016/j.phrs.2020.105264 Doi:.
Men, T.T., Phien, H.H., Tu Ai, T.T., Van Ay, N., Kim Hue, N.T., Khang, D.T., et al. The insecticidal capacity of ethanol extract from Cascabela peruviana (L.) Lippold against fruit fly. Heliyon, 8, 2022, e09313, 10.1016/j.heliyon.2022.e09313 Doi:.
Meshitsuka, S., Shingaki, S., Hotta, M., Goto, M., Kobayashi, M., Ukawa, Y., et al. Phase 2 trial of daily, oral epigallocatechin gallate in patients with light-chain amyloidosis. Int. J. Hematol. 105 (2017), 295–308, 10.1007/s12185-016-2112-1 Doi:.
Miranda, R.S., de Jesus, B., da Silva Luiz, S.R., Viana, C.B., Adao Malafaia, C.R., Figueiredo, F.S., et al. Antiinflammatory activity of natural triterpenes-An overview from 2006 to 2021. Phytother. Res., 2022, 10.1002/ptr.7359 Doi:.
Moher, D., Shamseer, L., Clarke, M., Ghersi, D., Liberati, A., Petticrew, M., et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst. Rev., 4, 2015, 1, 10.1186/2046-4053-4-1 Doi:.
Moresco, K.S., Silveira, A.K., Schnorr, C.E., Zeidán-Chuliá, F., Bortolin, R.C., Bittencourt, L.D.S., et al. Supplementation with Achyrocline satureioides inflorescence extracts to pregnant and breastfeeding rats induces tissue-specific changes in enzymatic activity and lower neonatal survival. Biomedicines, 5, 2017, 10.3390/biomedicines5030053 Doi:.
Mukherjee, P.K., Banerjee, S., Kar, A., Exploring synergy in ayurveda and traditional Indian systems of medicine. Synergy 7 (2018), 30–33, 10.1016/j.synres.2018.10.003 Doi:.
Murota, K., Nakamura, Y., Uehara, M., Flavonoid metabolism: the interaction of metabolites and gut microbiota. Biosci. Biotechnol. Biochem. 82 (2018), 600–610, 10.1080/09168451.2018.1444467 Doi:.
Obluchinskaya, E.D., Pozharitskaya, O.N., Zakharova, L.V., Daurtseva, A.V., Flisyuk, E.V., Shikov, A.N., Efficacy of natural deep eutectic solvents for extraction of hydrophilic and lipophilic compounds from Fucus vesiculosus. Molecules, 26, 2021, 10.3390/molecules26144198 Doi:.
Osbourn, A.E., Lanzotti, V., Plant-derived Natural Products: Synthesis, Function, and Application. 2009, Springer, Dordrecht Heidelberg London New York, 10.1007/978-0-387-85498-4 Doi:.
Page, M.J., McKenzie, J.E., Bossuyt, P.M., Boutron, I., Hoffmann, T.C., Mulrow, C.D., et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Revista espanola de cardiologia (English ed.) 74 (2021), 790–799, 10.1016/j.rec.2021.07.010 Doi:.
Pam, D., Etuh, A.M., Oyeniran, O.I., Mdekere, I.W., Toxicity of Mangifera Indica aqueous stem bark extract evaluated in drosophila melanogaster used as model organism. Ann. Pharm. Fr. 79 (2021), 539–546, 10.1016/j.pharma.2021.02.005 Doi:.
Pan, H., Hu, Q., Wang, J., Liu, Z., Wu, D., Lu, W., et al. Myricetin is a novel inhibitor of human inosine 5′-monophosphate dehydrogenase with anti-leukemia activity. Biochem. Biophys. Res. Commun. 477 (2016), 915–922, 10.1016/j.bbrc.2016.06.158 Doi:.
Panossian, A., Seo, E.-J., Efferth, T., Synergy assessments of plant extracts used in the treatment of stress and aging-related disorders. Synergy 7 (2018), 39–48, 10.1016/j.synres.2018.10.001 Doi:.
Pasdar, Y., Oubari, F., Zarif, M.N., Abbasi, M., Pourmahmoudi, A., Hosseinikia, M., Effects of quercetin supplementation on hematological parameters in Non-Alcoholic fatty liver disease: a randomized, double-blind, placebo-controlled pilot study. Clin. Nutr. Res., 9, 2020, 11, 10.7762/cnr.2020.9.1.11 Doi:.
Perera, N., Liolitsa, D., Iype, S., Croxford, A., Yassin, M., Lang, P., et al. Phlebotonics for haemorrhoids. Cochrane Database Syst. Rev., 2012, 10.1002/14651858.CD004322.pub3 Doi:.
Peter, K., Liu, J., Shi, D., Zhang, L., Dong, G., Zhang, D., et al. Improvement of early ventricular remodeling after myocardial infarction by a modified traditional Chinese medicine sini decoction. Eur. J. Integrat. Med., 6, 2014, 132, 10.1016/j.eujim.2013.12.016 Doi:.
Petrussa, E., Braidot, E., Zancani, M., Peresson, C., Bertolini, A., Patui, S., et al. Plant flavonoids–biosynthesis, transport and involvement in stress responses. Int. J. Mol. Sci. 14 (2013), 14950–14973, 10.3390/ijms140714950 Doi:.
Petruzzellis, V., Troccoli, T., Candiani, C., Guarisco, R., Lospalluti, M., Belcaro, G., et al. Oxerutins (Venoruton): efficacy in chronic venous insufficiency–a double-blind, randomized, controlled study. Angiology 53 (2002), 257–263, 10.1177/000331970205300302 Doi:.
Peyrat-Maillard, M.N., Cuvelier, M.E., Berset, C., Antioxidant activity of phenolic compounds in 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced oxidation: Synergistic and antagonistic effects. J. Am. Oil Chem. Soc., 80, 2003, 1007, 10.1007/s11746-003-0812-z Doi:.
Pferschy-Wenzig, E.M., Koskinen, K., Moissl-Eichinger, C., Bauer, R., A combined LC-MS metabolomics- and 16S rRNA sequencing platform to assess interactions between herbal medicinal products and human gut bacteria in vitro: a pilot study on willow bark extract. Front. Pharmacol., 8, 2017, 893, 10.3389/fphar.2017.00893 Doi:.
Pozharitskaya, O.N., Shikov, A.N., Kosman, V.M., Selezneva, A.I., Urakova, I.N., Makarova, M.N., et al. Immunomodulatory and antioxidants properties of fixed combination of fish oil with plant extracts. Synergy 2 (2015), 19–24, 10.1016/j.synres.2015.07.001 Doi:.
Qin, N., Xu, G., Wang, Y., Zhan, X., Gao, Y., Wang, Z., et al. Bavachin enhances NLRP3 inflammasome activation induced by ATP or nigericin and causes idiosyncratic hepatotoxicity. Front. Med. 15 (2021), 594–607, 10.1007/s11684-020-0809-2 Doi:.
Rastegarpanah, M., Malekzadeh, R., Vahedi, H., Mohammadi, M., Elahi, E., Chaharmahali, M., et al. A randomized, double blinded, placebo-controlled clinical trial of silymarin in ulcerative colitis. Chin. J. Integr. Med. 21 (2015), 902–906, 10.1007/s11655-012-1026-x Doi:.
Robertson, N., Schooness, A., Brand, A., Visser, J., Pine bark (Pinus spp.) extract for treating chronic disorders. Cochrane Database Systematic Rev.(9), 2020, CD008294, 10.1002/14651858.CD008294.pub5 IssueArt. No.:Doi:.
Scallon, C., Bell-Syer, S., Aziz, Z., Flavonoids for treating venous leg ulcers. Cochrane Database of Systematic Rev, Issue 5. Art. No.: CD006477., 2013, 10.1002/14651858.CD006477.pub2 Doi:.
Sekirov, I., Russell, S.L., Antunes, L.C., Finlay, B.B., Gut microbiota in health and disease. Physiol. Rev. 90 (2010), 859–904, 10.1152/physrev.00045.2009 Doi:.
Senger, M.R., Fraga, C.A., Dantas, R.F., Silva, F.P. Jr., Filtering promiscuous compounds in early drug discovery: is it a good idea?. Drug Discov. Today 21 (2016), 868–872, 10.1016/j.drudis.2016.02.004 Doi:.
Shanafelt, T.D., Call, T.G., Zent, C.S., Leis, J.F., LaPlant, B., Bowen, D.A., et al. Phase 2 trial of daily, oral Polyphenon E in patients with asymptomatic, Rai stage 0 to II chronic lymphocytic leukemia. Cancer 119 (2013), 363–370, 10.1002/cncr.27719 Doi:.
Singh, A., Cullen, J.K., Bruce, Z.C., Reddell, P., Münch, G., Raju, R., Ternstroenols A - E: Undescribed pentacyclic triterpenoids from the Australian rainforest plant Ternstroemia cherryi. Phytochemistry, 176, 2020, 112426, 10.1016/j.phytochem.2020.112426 Doi:.
Skroza, D., Generalić Mekinić, I., Svilović, S., Šimat, V., Katalinić, V., Investigation of the potential synergistic effect of resveratrol with other phenolic compounds: a case of binary phenolic mixtures. J. Food Compos. Anal. 38 (2015), 13–18, 10.1016/j.jfca.2014.06.013 Doi:.
Sparg, S.G., Light, M.E., van Staden, J., Biological activities and distribution of plant saponins. J. Ethnopharmacol. 94 (2004), 219–243, 10.1016/j.jep.2004.05.016 Doi:.
Su, H.X., Yao, S., Zhao, W.F., Li, M.J., Liu, J., Shang, W.J., et al. Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients. Acta Pharmacol. Sin. 41 (2020), 1167–1177, 10.1038/s41401-020-0483-6 Doi:.
Suardi, N., Gandaglia, G., Nini, A., Montorsi, F., Pellucchi, F., Agostini, A., et al. Effects of Difaprost® on voiding dysfunction, histology and inflammation markers in patients with benign prostatic hyperplasia who are candidates for surgical treatment. Minerva Urol. Nefrol. 66 (2014), 119–125 Doi:.
Subramani, B., Sathiyarajeswaran, P., Current update on herbal sources of antithrombotic activity-a comprehensive review. Egypt. J. Intern. Med., 34, 2022, 26, 10.1186/s43162-021-00090-9 Doi:.
Tatti, S., Swinehart, J.M., Thielert, C., Tawfik, H., Mescheder, A., Beutner, K.R., Sinecatechins, a defined green tea extract, in the treatment of external anogenital warts: a randomized controlled trial. Obstet. Gynecol. 111 (2008), 1371–1379, 10.1097/AOG.0b013e3181719b60 Doi:.
Tonelli, C.A., de Oliveira, S.Q., Silva Vieira, A.A.D., Biavatti, M.W., Ritter, C., Reginatto, F.H., et al. Clinical efficacy of capsules containing standardized extract of Bauhinia forficata Link (pata-de-vaca) as adjuvant treatment in type 2 diabetes patients: A randomized, double blind clinical trial. J. Ethnopharmacol., 282, 2022, 114616, 10.1016/j.jep.2021.114616 Doi:.
Vanhees, K., de Bock, L., Godschalk, R.W., van Schooten, F.J., van Waalwijk van Doorn-Khosrovani, S.B., Prenatal exposure to flavonoids: implication for cancer risk. Toxicol. Sci. 120 (2011), 59–67, 10.1093/toxsci/kfq388 Doi:.
Verpoorte, R., Kim, H.K., Choi, Y.H., Synergy: Easier to say than to prove. Synergy 7 (2018), 34–35, 10.1016/j.synres.2018.10.004 Doi:.
Voutquenne-Nazabadioko, L., Gevrenova, R., Borie, N., Harakat, D., Sayagh, C., Weng, A., et al. Triterpenoid saponins from the roots of Gypsophila trichotoma Wender. Phytochemistry 90 (2013), 114–127, 10.1016/j.phytochem.2013.03.001 Doi:.
Walle, T., Absorption and metabolism of flavonoids. Free Radic. Biol. Med. 36 (2004), 829–837, 10.1016/j.freeradbiomed.2004.01.002 Doi:.
Wang, C.Z., Du, G.J., Zhang, Z., Wen, X.D., Calway, T., Zhen, Z., et al. Ginsenoside compound K, not Rb1, possesses potential chemopreventive activities in human colorectal cancer. Int. J. Oncol. 40 (2012), 1970–1976, 10.3892/ijo.2012.1399 Doi:.
Wang, D., Wang, X.-H., Yu, X., Cao, F., Cai, X., Chen, P., et al. Pharmacokinetics of Anthraquinones from Medicinal Plants. Front. Pharmacol., 12, 2021, 638993, 10.3389/fphar.2021.638993 Doi:.
Wang, K., Lin, D., Guo, X., Huang, W., Peng, Y., Zheng, J., Chemical Identity of Interaction of Protein with Reactive Metabolite of Diosbulbin B In Vitro and In Vivo. Toxins, 9, 2017, 10.3390/toxins9080249 Doi:.
Wang, L., Lu, J., Zeng, Y., Guo, Y., Wu, C., Zhao, H., et al. Improving Alzheimer's disease by altering gut microbiota in tree shrews with ginsenoside Rg1. FEMS Microbiol. Lett., 367, 2020, 10.1093/femsle/fnaa011 Doi:.
Wang, M., Firrman, J., Liu, L., Yam, K., A review on flavonoid Apigenin: dietary intake, ADME, antimicrobial effects, and interactions with human gut microbiota. Biomed. Res. Int., 2019, 2019, 7010467, 10.1155/2019/7010467 Doi:.
Wang, R., Wei, L., Dong, Z., Meng, F., Wang, G., Zhou, S., et al. Pterocephin A, a novel Triterpenoid Saponin from Pterocephalus hookeri induced liver injury by activation of necroptosis. Phytomedicine, 85, 2021, 153548, 10.1016/j.phymed.2021.153548 Doi:.
Wang, X.X., Hou, J., Ning, J., Pan, Y.Q., Hong, M., Guo, B., Inhibition of sciadopitysin against UDP-glucuronosyltransferases. Yao Xue Xue Bao 51 (2016), 749–755, 10.16438/j.0513-4870.2015-0936 Doi:.
Wang, X.X., Lv, X., Li, S.Y., Hou, J., Ning, J., Wang, J.Y., et al. Identification and characterization of naturally occurring inhibitors against UDP-glucuronosyltransferase 1A1 in Fructus Psoraleae (Bu-gu-zhi). Toxicol. Appl. Pharmacol. 289 (2015), 70–78, 10.1016/j.taap.2015.09.003 Doi:.
Wei, M.-p., Yu, H., Guo, Y.-h., Cheng, Y.-l., Xie, Y.-f., Yao, W.-r., Antibacterial activity of Sapindus saponins against microorganisms related to food hygiene and the synergistic action mode of Sapindoside A and B against Micrococcus luteus in vitro. Food Control, 130, 2021, 108337, 10.1016/j.foodcont.2021.108337 Doi:.
Wei, M.-p., Yu, H., Guo, Y.-h., Cheng, Y.-l., Xie, Y.-f., Yao, W.-r., Potent in vitro synergistic antibacterial activity of natural amphiphilic Sapindoside A and B against Cutibacterium acnes with destructive effect on bacterial membrane. Biochim. Biophys. Acta Biomembr., 1863, 2021, 183699, 10.1016/j.bbamem.2021.183699 Doi:.
Wei, M.P., Yu, H., Guo, Y.H., Cheng, Y.L., Xie, Y.F., Yao, W.R., Synergistic antibacterial combination of Sapindoside A and B changes the fatty acid compositions and membrane properties of Cutibacterium acnes. Microbiol. Res., 255, 2021, 126924, 10.1016/j.micres.2021.126924 Doi:.
Wei, T.T., Chandy, M., Nishiga, M., Zhang, A., Kumar, K.K., Thomas, D., et al. Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation. Cell, 2022, 10.1016/j.cell.2022.04.005 Doi:.
Wetzel, D., Menke, W., Dieter, R., Smasal, V., Giannetti, B., Bulitta, M., Escin/diethylammonium salicylate/heparin combination gels for the topical treatment of acute impact injuries: a randomised, double blind, placebo controlled, multicentre study. Br. J. Sports Med. 36 (2002), 183–188, 10.1136/bjsm.36.3.183 Doi:.
Wisløff, H., Uhlig, S., Scheie, E., Loader, J., Wilkins, A., Flåøyen, A., Toxicity testing of saponin-containing Yucca schidigera Roetzl. juice in relation to hepato- and nephrotoxicity of Narthecium ossifragum (L.) Huds. Toxicon 51 (2008), 140–150, 10.1016/j.toxicon.2007.08.016 Doi:.
Xie, F., Su, M., Qiu, W., Zhang, M., Guo, Z., Su, B., et al. Kaempferol promotes apoptosis in human bladder cancer cells by inducing the tumor suppressor. PTEN. Int. J. Mol. Sci. 14 (2013), 21215–21226, 10.3390/ijms141121215 Doi:.
Xu, J., Li, S., Jiang, L., Gao, X., Liu, W., Zhu, X., et al. Baicalin protects against zearalenone-induced chicks liver and kidney injury by inhibiting expression of oxidative stress, inflammatory cytokines and caspase signaling pathway. Int. Immunopharmacol., 100, 2021, 108097, 10.1016/j.intimp.2021.108097 Doi:.
Xu, T., Zhang, S., Zheng, L., Yin, L., Xu, L., Peng, J., A 90-day subchronic toxicological assessment of dioscin, a natural steroid saponin, in Sprague-Dawley rats. Food Chem. Toxicol. 50 (2012), 1279–1287, 10.1016/j.fct.2012.02.027 Doi:.
Yan, D., Zheng, G., Wang, C., Chen, Z., Mao, T., Gao, J., et al. HIT 2.0: an enhanced platform for herbal Ingredients' targets. Nucl. Acids. Res. 50 (2021), D1238–D1243, 10.1093/nar/gkab1011 Doi:.
Yang, B., Yang, H., Chen, F., Hua, Y., Jiang, Y., Phytochemical analyses of Ziziphus jujuba Mill. var. spinosa seed by ultrahigh performance liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Analyst 138 (2013), 6881–6888, 10.1039/c3an01478a Doi:.
Yang, C., Lim, W., Bazer, F.W., Song, G., Myricetin suppresses invasion and promotes cell death in human placental choriocarcinoma cells through induction of oxidative stress. Cancer Lett. 399 (2017), 10–19, 10.1016/j.canlet.2017.04.014 Doi:.
Yang, L., Zou, H., Gao, Y., Luo, J., Xie, X., Meng, W., et al. Insights into gastrointestinal microbiota-generated ginsenoside metabolites and their bioactivities. Drug Metab. Rev. 52 (2020), 125–138, 10.1080/03602532.2020.1714645 Doi:.
Yang, N., Li, C., Li, H., Liu, M., Cai, X., Cao, F., et al. Emodin Induced SREBP1-dependent and SREBP1-Independent apoptosis in hepatocellular carcinoma cells. Front. Pharmacol., 10, 2019, 709, 10.3389/fphar.2019.00709 Doi:.
Yang, X., Zhang, H., Synergistic interaction of tea saponin with mancozeb against Pestalotiopsis theae. Crop Protect. 40 (2012), 126–131, 10.1016/j.cropro.2012.04.013 Doi: doi.org/.
Yang, Y., Zhang, Z., Li, S., Ye, X., Li, X., He, K., Synergy effects of herb extracts: pharmacokinetics and pharmacodynamic basis. Fitoterapia 92 (2014), 133–147, 10.1016/j.fitote.2013.10.010 Doi:.
Yao, W., Cheng, J., Kandhare, A.D., Mukherjee-Kandhare, A.A., Bodhankar, S.L., Lu, G., Toxicological evaluation of a flavonoid, chrysin: morphological, behavioral, biochemical and histopathological assessments in rats. Drug Chem. Toxicol. 44 (2021), 601–612, 10.1080/01480545.2019.1687510 Doi:.
Yoshimura, M., Enomoto, T., Dake, Y., Okuno, Y., Ikeda, H., Cheng, L., et al. An evaluation of the clinical efficacy of tomato extract for perennial allergic rhinitis. Allergol Int 56 (2007), 225–230, 10.2332/allergolint.O-06-443 Doi:.
You, Y.L., Ling, C.Q., Feng, Y.L., Efficacy of combined therapy with ginsenosides and prednisone in treating systemic lupus erythematosus–a randomized, controlled and double-blinded trial. Zhongguo Zhong Xi Yi Jie He Za Zhi 29 (2009), 776–779 Doi:.
Yu, H., Zhang, W.L., Ding, X., Zheng, K.Y., Ho, C.M., Tsim, K.W., et al. Optimizing combinations of flavonoids deriving from astragali radix in activating the regulatory element of erythropoietin by a feedback system control scheme. Evid. Based Compl. Alternat. Med., 2013, 2013, 541436, 10.1155/2013/541436 Doi:.
Yu, K., Chen, F., Li, C., Absorption, disposition, and pharmacokinetics of saponins from Chinese medicinal herbs: what do we know and what do we need to know more?. Curr. Drug Metab. 13 (2012), 577–598, 10.2174/1389200211209050577 Doi:.
Yuan, Y., Men, W., Shan, X., Zhai, H., Qiao, X., Geng, L., et al. Baicalein exerts neuroprotective effect against ischaemic/reperfusion injury via alteration of NF-kB and LOX and AMPK/Nrf2 pathway. Inflammopharmacology 28 (2020), 1327–1341, 10.1007/s10787-020-00714-6 Doi:.
Zahedi, M., Ghiasvand, R., Feizi, A., Asgari, G., Darvish, L., Does quercetin improve cardiovascular risk factors and inflammatory biomarkers in women with Type 2 diabetes: a double-blind randomized controlled clinical trial. Int. J. Prev. Med. 4 (2013), 777–785 Doi:.
Zeng, X., Xi, Y., Jiang, W., Protective roles of flavonoids and flavonoid-rich plant extracts against urolithiasis: a review. Crit. Rev. Food Sci. Nutr. 59 (2019), 2125–2135, 10.1080/10408398.2018.1439880 Doi:.
Zeng, X., Zhang, P., He, W., Qin, C., Chen, S., Tao, L., et al. NPASS: natural product activity and species source database for natural product research, discovery and tool development. Nucl. Acids. Res. 46 (2017), D1217–D1222, 10.1093/nar/gkx1026 Doi:.
Zhang, H.W., Zhang, H., Grant, S.J., Wan, X., Li, G., Single herbal medicine for diabetic retinopathy. Cochrane Database of Systematic Rev. Issue 12. Art., 2018, CD007939, 10.1002/14651858.CD007939.pub2 Doi:.
Zhang, R., Zhai, Q., Yu, Y., Li, X., Zhang, F., Hou, Z., et al. Safety assessment of crude saponins from Chenopodium quinoa willd. husks: 90-day oral toxicity and gut microbiota & metabonomics study in rats. Food Chem., 375, 2022, 131655, 10.1016/j.foodchem.2021.131655 Doi:.
Zhang, S., Wang, Y., Yu, M., Shang, Y., Chang, Y., Zhao, H., et al. Discovery of Herbacetin as a Novel SGK1 Inhibitor to Alleviate Myocardial Hypertrophy. Adv. Sci. (Weinh.), 9, 2022, e2101485, 10.1002/advs.202101485 Doi:.
Zhou, M., Wang, S., Zhao, A., Wang, K., Fan, Z., Yang, H., et al. Transcriptomic and metabonomic profiling reveal synergistic effects of quercetin and resveratrol supplementation in high fat diet fed mice. J. Proteome Res. 11 (2012), 4961–4971, 10.1021/pr3004826 Doi:.
Zhou, S., Yin, X., Yuan, J., Liang, Z., Song, J., Li, Y., et al. Antifibrotic activities of Scutellariae Radix extracts and flavonoids: Comparative proteomics reveals distinct and shared mechanisms. Phytomedicine, 100, 2022, 154049, 10.1016/j.phymed.2022.154049 Doi:.
Zhuang, J., Peng, Y., Gu, C., Chen, H., Lin, Z., Zhou, H., et al. Wogonin accelerates hematoma clearance and improves neurological outcome via the PPAR-gamma pathway after intracerebral hemorrhage. Transl. Stroke Res. 12 (2021), 660–675, 10.1007/s12975-020-00842-9 Doi:.
Zhuo, Y., Zhang, Y., Li, M., Wu, H., Gong, S., Hu, X., et al. Hepatotoxic evaluation of toosendanin via biomarker quantification and pathway mapping of large-scale chemical proteomics. Food Chem. Toxicol., 153, 2021, 112257, 10.1016/j.fct.2021.112257 Doi:.
