Cnidium officinale Makino: Phytology, Phytochemistry, Toxicology, Pharmacology and Prescriptions (1967-2023).

Cnidium officinale Makino (COM), a perennial herbaceous plant in the Apiaceous family, widely distribute in Eastern Asia and Asia-Temperate. It has a long history application as a traditional medicine for invigorating the blood and removing blood stasis, and also has been employed to diet, pesticide, herbal bathing materials, the cosmetic and skin care industry. However, there has been no associated review of literature in the past half a century (1967-2023). By searching the international authoritative databases and collecting 229 literatures closely related to COM, herewith a comprehensive and systematic review was conducted. The phytology includes plant distribution and botanical characteristics. The phytochemistry covers 8 major categories, 208 compounds in total, and the quantitative determination of 14 monomer compounds, total polyphenols and total flavonoids. The clinical trial in pregnant women and toxic experiments in mice, the pharmacology of 7 aspects and 82 frequently used prescriptions are summarized. It is expected that this paper will provide forward-looking scientific thinking and literature support for the further modern research, development and utilization of COM.

Kalopanax septemlobus: its phytochemistry, pharmacology and toxicity (1966-2022).

Kalopanax septemlobus is a traditional herbal medicine for multiple medicinal sites (root, stem bark, bark, leaves) in East Asia, and its bark has a significant curative effect on rheumatoid arthritis. In the past 13 years (2009-2022), the research literature accounted for 50% of the total, and it is becoming a research highlight of the relevant international scholars (ACS, ScienceDirect, PubMed, Springer, and Web of Science). This paper is the first comprehensive review of its chemistry, pharmacology, and toxicity for more than half a century (1966-2022), in which the chemical studies include triterpenoids & saponins (86 compounds), and phenylpropanoids (26 compounds), involving 46 new structures and one biomarker-triterpenoid saponin (Kalopanaxsaponin A); According to the number of literature, the pharmacological effects and mechanisms are systematically divided into five aspects, such as: anti-inflammatory, anti-tumor, antioxidant, antifungal and anti-diabetic, etc., covering its toxicological progress. To provide literature support for the exploration of new drugs against related diseases, such as rheumatoid arthritis, which are becoming younger nowadays.

Study on HPLC Fingerprint, Network Pharmacology, and Antifungal Activity of Rumex japonicus Houtt.

BACKGROUND: Rumex japonicus Houtt (R. japonicus) is used mainly to treat various skin diseases in Southeast Asia. However, there are few studies on its quality evaluation methods and antifungal activity. OBJECTIVE: To establish the quality control criteria for the effective parts from R. japonicus against psoriasis. METHODS: High-performance liquid chromatography (HPLC) was established for its fingerprint, and the similarity evaluation, cluster analysis (CA) and principal component analysis (PCA) were used to reveal the differences of those fingerprints among the tested R. japonicus. Network pharmacology analyzed the relationship between the components and psoriasis, revealing the potential targets of R. japonicus. Oxford cup anti-C. albicans experiment was used to verify the antifungal activity of R. japonicus. RESULTS: HPLC was developed for the R. japonicus fingerprint by optimizing for 10 batches of quinquennial R. japonicus from different habitats; the 18 common peaks were identified with 10 characteristic peaks such as rutin, quercetin, aloe-emodin, nepodin, emodin, musizin-8-O-ß-D-glucoside, chrysophanol, emodin-8-O-ß-D-glucopyranoside, chrysophanol-8-O-ß-D-glucopyranoside, and aloin, respectively. The network pharmacology-based analysis showed a high correlation between R. japonicus and psoriasis, revealing the potential targets of R. japonicus. The oxford cup anti-Candida albicans experiment displayed a significant activity response to emodin-8-O-ß-D-glucopyranoside and the ethyl acetate fraction of R. japonicus acidic aqueous extract. CONCLUSIONS: A new and optimized HPLC method was created, and the research provides an experimental basis for the development of effective drugs related to C. albicans. HIGHLIGHTS: The fingerprint of R. japonicus was organically combined with network pharmacology to further clarify its criteria for quality control.

Study on chemical constituents of Folium Artemisiae argyi Carbonisatum, toxicity evaluation on zebrafish and intestinal hemostasis.

Folium Artemisiae argyi Carbonisatum (FAAC) is a traditional medicine widely used in clinic. It has the effect of hemostasis by warming meridians. In order to further explore the chemical composition and biological activity of FAAC, the methanol extract of FAAC was isolated and purified by open column and high- performance liquid chromatography. and the complete structure was characterized by nuclear magnetic resonance (NMR) and LREI-MS for the first time, namely rutin, quercetin and octacosanol respectively. Initially the toxic effect of methanol extract of FAAC on zebrafish was evaluated by observing the phenotypic characteristics, spontaneous twitch times, heart rate, hatching rate, the distance of SV-BA and cardiomyocyte apoptosis of zebrafish. The results showed that FAAC has embryonic development toxicity and cardiotoxicity when it was higher than 62.5 µg/mL. Meanwhile, the hemostatic effect of methanol extract of FAAC was compared with FAA (Folium Artemisia argyi) by zebrafish intestinal bleeding model originally. The results showed that the hemostatic effect of the medium and high concentration dose groups (3.0 and 30.0 µg/mL) was enhanced for both FAAC and FAA. This study provided an experimental basis for the clinical application of FAAC.

Genus Suaeda: Advances in phytology, chemistry, pharmacology and clinical application (1895 - 2021).

More than 100 species of annual herb genus Suaeda widely distribute (Asia, North America, northern Africa and Europe), are rich in resources (about hundreds of millions of tons/Y) and have a long historical application. Most of them are mainly used for traditional food, feed and medicine. Recently, they have been employed to repair saline-alkali land and beautify the environment. So far, only 27 species have been reported on the bioactivity diversity, broad spectrum and effectiveness in clinical practice. Therefore, the in-depth and extensive research of Suaeda has become a research hotspot around the world. However, only one review summarized the nutritional, chemical and biological values of Suaeda. By searching the international authoritative databases (ACS Publications, ScienceDirect, PubMed, Springer, web of Science and Bing International etc.) and collecting 103 literatures closely related to Suaeda (1895-2021), herewith a comprehensive and systematic review was conducted on the phytology, chemistry, pharmacology and clinical application, enveloping the classification evolution between Amaranthaceae and Chenopodiaceae, distribution and common botanical characteristics; involving 9 chemical categories of 163 derivatives covering 14 new and 6 first-isolated ones, and appraising the content determination of 6 categories of components; mainly including the pharmacology of 13 species in vivo and vitro; estimating the clinical application of 16 species cured the related diseases of eight human physiological system except for the motor system. It is expected that this paper will provide forward-looking scientific ideas and literature support for the further modern research, development and utilization of the genus.

Glucosamine promotes hepatitis B virus replication through its dual effects in suppressing autophagic degradation and inhibiting MTORC1 signaling.

Glucosamine (GlcN), a dietary supplement widely utilized to promote joint health and effective in the treatment of osteoarthritis, is an effective macroautophagy/autophagy activator in vitro and in vivo. Previous studies have shown that autophagy is required for hepatitis B virus (HBV) replication and envelopment. The objective of this study was to determine whether and how GlcN affects HBV replication, using in vitro and in vivo experiments. Our data demonstrated that HBsAg production and HBV replication were significantly increased by GlcN treatment. Confocal microscopy and western blot analysis showed that the amount of autophagosomes and the levels of autophagic markers MAP1LC3/LC3-II and SQSTM1 were clearly elevated by GlcN treatment. GlcN strongly blocked autophagic degradation of HBV virions and proteins by inhibiting lysosomal acidification through its amino group. Moreover, GlcN further promoted HBV replication by inducing autophagosome formation via feedback inhibition of mechanistic target of rapamycin kinase complex 1 (MTORC1) signaling in an RRAGA (Ras related GTP binding A) GTPase-dependent manner. In vivo, GlcN application promoted HBV replication and blocked autophagic degradation in an HBV hydrodynamic injection mouse model. In addition, GlcN promoted influenza A virus, enterovirus 71, and vesicular stomatitis virus replication in vitro. In conclusion, GlcN efficiently promotes virus replication by inducing autophagic stress through its dual effects in suppressing autophagic degradation and inhibiting MTORC1 signaling. Thus, there is a potential risk of enhanced viral replication by oral GlcN intake in chronically virally infected patients.Abbreviations: ACTB: actin beta; ATG: autophagy-related; CMIA: chemiluminescence immunoassay; ConA: concanavalin A; CQ: chloroquine; CTSD: cathepsin D; DAPI: 4',6-diamidino-2-phenylindole; EV71: enterovirus 71; GalN: galactosamine; GFP: green fluorescence protein; GlcN: glucosamine; GNPNAT1: glucosamine-phosphate N-acetyltransferase 1; HBP: hexosamine biosynthesis pathway; HBV: hepatitis B virus; HBcAg: hepatitis B core antigen; HBsAg: hepatitis B surface antigen; HBeAg: hepatitis B e antigen; HBV RI: hepatitis B replicative intermediate; IAV: influenza A virus; LAMP1: lysosomal associated membrane protein 1; LAMTOR: late endosomal/lysosomal adaptor, MAPK and MTOR activator; ManN: mannosamine; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTORC1: mechanistic target of rapamycin kinase complex 1; PHH: primary human hepatocyte; RAB7: RAB7A, member RAS oncogene family; RPS6KB1: ribosomal protein S6 kinase B1; RRAGA: Ras related GTP binding A; RT-PCR: reverse transcriptase polymerase chain reaction; SEM: standard error of the mean; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; UAP1: UDP-N-acetylglucosamine pyrophosphorylase 1; VSV: vesicular stomatitis virus.

Identification of Steroidogenic Components Derived From Gardenia jasminoides Ellis Potentially Useful for Treating Postmenopausal Syndrome.

Estrogen-stimulating principles have been demonstrated to relieve postmenopausal syndrome effectively. Gardenia jasminoides Ellis (GJE) is an herbal medicine possessing multiple pharmacological effects on human health with low toxicity. However, the therapeutic effects of GJE on the management of postmenopausal syndrome and its mechanism of action have not been fully elucidated. In this study, network pharmacology-based approaches were employed to examine steroidogenesis under the influence of GJE. In addition, the possibility of toxicity of GJE was ruled out and four probable active compounds were predicted. In parallel, a chromatographic fraction of GJE with estrogen-stimulating effect was identified and nine major compounds were isolated from this active fraction. Among the nine compounds, four of them were identified by network pharmacology, validating the use of network pharmacology to predict active compounds. Then the phenotypic approaches were utilized to verify that rutin, chlorogenic acid (CGA) and geniposidic acid (GA) exerted an estrogen-stimulating effect on ovarian granulosa cells. Furthermore, the results of target-based approaches indicated that rutin, CGA, and GA could up-regulate the FSHR-aromatase pathway in ovarian granulosa cells. The stimulation of estrogen production by rat ovarian granulosa cells under the influence of the three compounds underwent a decline when the follicle-stimulating hormone receptor (FSHR) was blocked by antibodies against the receptor, indicating the involvement of FSHR in the estradiol-stimulating activity of the three compounds. The effects of the three compounds on estrogen biosynthesis- related gene expression level were further confirmed by Western blot assay. Importantly, the MTT results showed that exposure of breast cancer cells to the three compounds resulted in reduction of cell viability, demonstrating the cytotoxicity of the three compounds. Collectively, rutin, chlorogenic acid and geniposidic acid may contribute to the therapeutic potential of GJE for the treatment of postmenopausal syndrome.

Inhibiting STAT3 signaling is involved in the anti-melanoma effects of a herbal formula comprising Sophorae Flos and Lonicerae Japonicae Flos.

A herbal formula (SL) comprising Sophorae Flos and Lonicerae Japonicae Flos was traditionally used to treat melanoma. Constitutively active signal transducer and activator of transcription 3 (STAT3) has been proposed as a therapeutic target in melanoma. Here we investigated whether an ethanolic extract of SL (SLE) exerted anti-melanoma activities by inhibiting STAT3 signaling. B16F10 allograft model, A375 and B16F10 cells were employed to assess the in vivo and in vitro anti-melanoma activities of SLE. A375 cells stably expressing STAT3C, a constitutively active STAT3 mutant, were used to determine the role of STAT3 signaling in SLE's anti-melanoma effects. Intragastric administration of SLE (1.2 g/kg) potently inhibited melanoma growth in mice and inhibited STAT3 phosphorylation in the tumors. In cultured cells, SLE dramatically reduced cell viability, induced apoptosis, suppressed migration and invasion, and restrained STAT3 activation and nuclear localization. STAT3C overexpression in A375 cells diminished SLE's effects on cell viability, apoptosis and invasion. Collectively, SLE exerted potent anti-melanoma effects partially by inhibiting STAT3 signaling. This study provides pharmacological justification for the traditional use of this formula in treating melanoma, and suggests that SLE has the potential to be developed as a modern alternative and/or complimentary agent for melanoma treatment and prevention.