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Background. Magnolia officinalis Rehd. and Wils. is widely used in Asian countries because of its multiple pharmacological effects. This study investigated the gastroprotective effect and mechanisms of the ethanol extracts from the bark of Magnolia officinalis (MOE) against ethanol-induced gastric mucosal damage in rats. Methods. MOE was prepared by reflux extraction with 70% ethanol, and its main compounds were analyzed by UPLC-Q-Exactive Orbitrap-MS. DPPH, ABTS, and FRAP methods were used to evaluate the antioxidant capacity of MOE in vitro. The gastroprotective effects of MOE were evaluated by the area of gastric injury, H&E (hematoxylin-eosin), and PAS (periodic acid-Schiff). The mechanism was explored by measuring the levels of cytokines and protein in the NF-κB signaling pathway. Results. 30 compounds were identified from MOE, mainly including lignans and alkaloids. MOE presented a high antioxidant activity in several oxidant in vitro systems. Gastric ulcer index and histological examination showed that MOE reduced ethanol-induced gastric mucosal injury in a dose-dependent manner. MOE pretreatment significantly restored the depleted activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) enzymes, reduced malondialdehyde (MDA), and prostaglandin E2 (PGE2) levels in the gastric tissue in rats. In addition, MOE also inhibited the activation of nuclear factor kappa B (NF-κB) pathway and decreased the production of proinflammatory cytokines. Conclusions. The gastroprotective effect of MOE was attributed to the inhibition of oxidative stress and the NF-κB inflammatory pathway. The results provided substantial evidence that MOE could be a promising phytomedicine for gastric ulcer prevention.

Context Processing with vinegar could enhance the efficacy and reduce the toxicity of Curcuma phaeocaulis Valeton. (Zingiberaceae), a Chinese herbal medicine with anti-inflammatory and antitumor activities. Objective This study investigated the vinegar processing effects by evaluating anti-angiogenic effect and toxicity of C. phaeocaulis through zebrafish and rat models. Materials and methods Zebrafish embryos (AB and FLk-GFP strain) were applied to evaluate toxicity, cardiotoxicity and anti-angiogenic activity of volatile oil, and water decoction of the raw and vinegar-processed C. phaeocaulis. Meanwhile, a blood stasis syndrome rat model was applied to study the toxicity by measuring the ovarian and uterine coefficient. Results Curcuma phaeocaulis volatile oil and its vinegar-processed products in zebrafish had an LC50 of 67.315 and 95.755 μg/mL, respectively. Curcuma phaeocaulis water decoction and its vinegar-processed products had an LC50 of 161.440 and 206.239 μg/mL, respectively. The toxicity of vinegar-processed products was significantly lower than the raw, and the development characteristic of zebrafish embryos at different times confirmed these results. The volatile oil of vinegar-processed products could inhibit the growth of intersegmental blood vessels at the dose of 20 μg/mL, while the raw materials did not exhibit such effect at the same concentration. The rat experiment also confirmed that the volatile oil could reduce toxicity of ovarian and uterine. Discussion and conclusions The study indicated that processing using vinegar could decrease toxicity and increase anti-angiogenic activity of C. phaeocaulis, which could be applied for clinical treatment. Further in-depth study on the synergism and detoxification mechanism of vinegar processing technology is needed.

Huangqin decoction (HQD), composed of Scutellaria(Huangqin), Peony(Shaoyao), Liquorice(Gancao) and Jujube(Dazao), is a traditional Chinese medicine prescription, originated from treatise on Febrile Diseases, has the functions of clearing heat, stopping benefits and relieving pain. It is the original prescription for treating heat and relieving dysentery, and is commonly used in clinic for diarrhea and other diseases. In ulcerative colitis, damp-heat syndrome is the most common. However, its mechanism of action is not completely clear.The purpose of the research is to investigate the protective effect of HQD on ulcerative colitis rats and the regulation effect of mitochondrial DNA, TLR4, p-Akt, p-PI3K protein and microbiota.The effects of HQD anti-UC were investigated by fluorescence quantitative PCR, cytokine level and histopathological analysis in DSS-induced ulcerative colitis (UC) rats. The content of mtDNA in colon epithelial cells of rats in each group was detected by fluorescence quantitative PCR, p-PI3K, p-Akt and TLR4 protein expressions in colon tissues of rats in each group were detected by Western blotting. IL-6, IL-17 and IL-23 inflammatory factors were detected by ELISA. The effect of HQD on intestinal microbiota of rats with ulcerative colitis was studied by high-throughput sequencing technology, and the correlation between mtDNA level and inflammatory factors as well as protein expression in colonic epithelium of rats with ulcerative colitis was analyzed by SPSS23.0.HQD significantly alleviated UC symptoms by improving the mucosal intestinal epithelial cell structure, mental state, hair gloss, fecal occult blood, lamina propria intestinal glands and inflammatory cell infiltration. And HQD reduced the pro-inflammatory cytokines in the colonic epithelium of UC rats Production of IL-6, IL-17 and IL-23. The HE stained section of colon tissue showed a complete intestinal epithelial mucosal layer structure. The structure of epithelial cells was more normal and abundant. There were more goblet cells in lamina propria adenoma, which improved the infiltration of inflammatory cells. HQD significantly inhibited the mtDNA content in rat colonic epithelial tissue, and significantly inhibited the expression of TLR4, p-PI3K and p-Akt inflammatory signaling pathways. The results of the microbiota experiment showed that the abundance of HQD in the phylum Firmicutes increased, and the number of Bacteroides phylum decreased (p 0.05). At the genus level, HQD significantly increased Lactobacillus and Firmicutes Bacteroides, while Treponema and Bacteroides were significantly reduced (p 0.05).HQD has a certain protective effect on rats with damp heat ulcerative colitis. Its mechanism may be related to regulating the expression of p-PI3K, p-Akt and TLR4 proteins, mitochondrial DNA as well as microbiota.

Ethnopharmacological relevance Shentong Zhuyu Decoction (STZYD) was first recorded in the classic of “Yilin Gaicuo” written by Wang Qingren, and recognized by the Chinese National Administration of Traditional Chinese Medicine as one of the 100 classic formulas. The formula has been widely used in the treatment of rheumatoid arthritis (RA) with significant clinical effects. However, its mechanism of action is not completely clear. Aim of the study This study aimed to explore the mechanism of STZYD in the treatment of RA by network pharmacology and metabolomic. Materials and methods The effects of STZYD anti-RA were investigated by paw swelling, arthritis score, cytokine level, histopathological and micro-CT analysis in adjuvant-induced arthritis (AIA) rats. The chemical constituents of STZYD and absorbed constituents in AIA rat serum were analyzed by UPLC-Q-Exactive MS/MS. Based on the characterized chemical components, the network pharmacology was used to find potential targets and signaling pathways of STZYD in RA treatment. Meanwhile, the predicted pathway was determined by the Western blot (WB). Subsequently, non-targeted metabolomics of serum was performed to analyze metabolic profiles, potential biomarkers, and metabolic pathways of STZYD in the treatment of RA based on LC-MS technology. Results STZYD significantly alleviated RA symptoms by improving paw redness and swelling, bone and cartilage damage, synovial hyperplasia, and infiltration of inflammatory cells, and decreased the generation of pro-inflammatory cytokines IL-1β, IL-6, IL-17A and TNF-α in AIA rats. Totally, 59 chemical components of STZYD and 24 serum migrant ingredients were identified. A total of 655 genes of potential bioactive components in STZYD and 1025 related genes of RA were obtained. TNF signaling pathway was considered to one of the main signaling pathways of STZYD anti-RA by KEGG analysis, including a wide range intracellular signaling pathways. NF-κB signaling pathway regulates inflammation and immunity in the TNF signaling pathway. STZYD markedly inhibited the expression of NF-κB signaling pathway. Ten potential biomarkers were found in metabolomics based on LC-MS technology. Alanine, aspartate and glutamate metabolism, arachidonic acid metabolism are the most related pathways of STZYD anti-RA. Conclusion The study based on serum pharmacochemistry, network pharmacology and metabolomics indicated that STZYD can improve RA through regulating inflammation and immunity related pathways, and provided a new possibility for treatment of RA.

Rhei Radix et Rhizoma was first recorded in Shennong Ben Cao Jing, with a wide range of pharmacological activities. Autoimmune disease is a kind of disease that damages the tissue structure and function of immune cells and their components due to the impairment of immune tolerance function, including atherosclerosis, multiple sclerosis, gout, rheumatoid arthritis, autoimmune thyroiditis, ulcerative colitis, type 1 diabetes and IgA nephropathy. In recent years, clinical and experimental studies show that Rhei Radix et Rhizoma has potential therapeutic effects on autoimmune diseases. Under the guidance of the theory of traditional Chinese medicine, this paper reviews therapeutic and intervening effects of Rhei Radix et Rhizoma and its main active ingredient anthraquinone on autoimmune diseases. It also puts forward new study directions in view of the existing problems in studies of rhubarb and its anthraquinone, with the aim to provide reference for clinical treatment and scientific studies of effect of Rhei Radix et Rhizomaon autoimmune diseases.

Six undescribed compounds, including four undescribed ecdysteroids (cyathsterones A-D) and two undescribed phenolic glycosides (cyathglucosides A-B), were isolated from the roots of Cyathula officinalis Kuan. Their structures were based on chemical analyses, NMR spectroscopic evidence, DP4+ calculations, and hydrolysis products. All compounds inhibited NO release in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages in vitro. Among them, cyathsterone A showed the strongest inhibitory effects. Moreover, cyathsterone A has been shown to inhibit the release of the proinflammatory cytokines TNF-α, IL-6, and IL-1β in LPS-induced RAW 264.7 macrophages in vitro. Further studies found that cyathsterone A present concentration-dependent suppression of the protein expression of iNOS and COX-2 in LPS-stimulated RAW 264.7 cells in vitro and exerted anti-inflammatory activity via the NF-κB signalling pathway.

Ethnopharmacological relevance Isatidis Radix (called Banlangen, BLG in Chinese) and Isatidis Folium (called Daqingye, DQY in Chinese) are common traditional edible-medicinal herbs in detoxifying for thousands of years, have been traditionally applied in traditional Chinese medicine for centuries. Both of them are bitter in taste, coolness in nature, acting on the heart and stomach channels. They are often used to treat influenza and other viral infectious diseases in clinic, as well as could treat fever, dizziness, and cough and sore throat caused by lung heat. Aims of the review This review aimed at summarizing the latest and comprehensive information of BLG and DQY on the ethnopharmacology, phytochemistry, pharmacology, toxicity and clinical application to explore the therapeutic potential of them. In addition, outlooks and perspective for possible future researches that related are also discussed. Materials and methods Related information concerning BLG and DQY were gathered from the internet database of Google Scholar, PubMed, Baidu Scholar, GeenMedical, CNKI and Web of Science, as well as other relevant textbooks, reviews, and documents (e.g., Chinese Pharmacopoeia, 2020 edition, Chinese herbal classic books and PhD and MSc thesis, etc.). Among of them with the keywords including “Isatis indigotica” “Isatidis Radix”, “Isatidis Folium”, “phytochemistry”, “pharmacology”, “toxicology”, “clinical application” etc. and their combinations. Results To date, 39 Chinese patent medicines containing BLG and/or DQY have been developed on basis of the data of NMPA. Besides, 304 and 142 compounds have been found in BLG and DQY, respectively. The main chemical differences between BLG and DQY were concentrated on alkaloids and lignans, such as indican, indirubin, (R, S)-epigoitrin, 4(3H)-quinazolinone, clemastanin B and isatindigotindolines A-D. In 2020 Edition ChP, (R, S)-goitrin and indirubin are now used as the official marker to monitor the quality of BLG and DQY, respectively. Modern pharmacology has mainly studied some monomer components such as 4(3H)-quinazolinone, clemastanin B, erucic acid and adenosine, etc., all of which have shown good effects. These active compounds can resist various viruses, such as influenza virus, respiratory syncytial virus, herpes simplex virus, etc.. By regulating the level of immunity and a variety of inflammatory factors, inhibit the growth and reproduction of the virus. At the same time, it is worth noting that different components of BLG and DQY lead to BLG is more powerful in antiviral and immunomodulatory activity than DQY, while DQY possesses a higher intensity than BLG in anti-oxidant activity. Conclusion By collecting and collating a large number of literature and various data websites, we concluded that the common compounds are mainly alkaloids. Recent findings regarding the phytochemical and pharmacological properties of BLG and DQY have confirmed their traditional uses in antiviral, antibacterial and treatment immune diseases. Without doubt, their significant differences on ethnopharmacology, phytochemistry and pharmacology can be used as evidence of separate list of BLG and DQY. For shortcomings, some comprehensive studies should be well designed for further utilization of BLG and DQY.

The EtOH extract of the roots of Platycodon grandiflorum afforded two new triterpene saponins platycoside P (1) and platycoside Q (2). Their structures were elucidated based on spectroscopic means and hydrolysis products. These compounds were evaluated for inhibitory activity against LPS-induced TNF-α production in RAW 246.7 macrophages. Compounds 1 and 2 showed inhibitory activity with the inhibition ratios (%) of 38.6 and 44.1 at 50 μM, respectively.

Cancer is a fatal disease with high mortality and low survival rate worldwide. At present, there is still no known cure for most cancers. Traditional Chinese medicine (TCM) represents a noteworthy reservoir for anticancer agents in drug discovery and development. Curcumae Rhizoma (called Ezhu in Chinese) is widely prescribed in TCM for anticancer therapy owing to its broad-spectrum antineoplastic activities. Especially, the terpenoids isolated from the essential oil of Curcumae Rhizoma form an integral part of cancer research and are well established as a potential anticancer agent. For example, β-elemene has been developed into a new drug for the treatment of solid tumors in China, and is currently undergoing clinical trials in the United States. The review aims to systematically summarize the recent advances on the anticancer effects and related molecular mechanisms of Curcumae Rhizoma, and its terpenoids (β-elemene, Furanodiene, Furanodienone, Germacrone, Curcumol, Curdione). In addition, we evaluated and compared the anticancer efficacy and clinical use of the terpenoids with combination therapies and traditional therapies. Therefore, this review provides sufficient evidence for the anticancer therapeutic potential of Curcumae Rhizoma and its terpenoids, and will contribute to the development of potential anticancer drugs.

Ethnopharmacological relevance Curcuma phaeocaulis Val. (CP), as the vital medicines for blood-breaking and disorder-eliminating, has been widely used for hepatitis with good curative effects. Owing to the complexity of traditional Chinese medicine, the pharmacological mechanism of CP remains unclear. To solve this problem, a protein network module-based approach was proposed in this study. Materials and methods Firstly, the content of active components of CP was detected based on HPLC-DAD. Then the liver protection of CP on Con A-induced hepatitis was validated via the analysis of serum levels of ALT, AST and LDH and histological findings. Next, the targets of CP components obtained from TCMD database were predicted by STITCH and ChEMBL retrieval. In addition, the protein interaction network (PIN) of CP was constructed by Cytoscape based on protein-protein interaction of targets obtained from STRING database. Following the topological analysis of CP PIN, it showed to exhibit the properties of scale-free, small world, and modularity matched with the property of complex biological networks. Finally, the functional modules were identified by gene ontology enrichment analysis based on Molecular Complex Detection algorithm. Results The functional modules indicated that the mechanism of CP acting on the hepatitis is significantly associated with NF-κB and TGF-β signaling pathway. More interestingly, curcumin, demethoxycurcumin and bisdemethoxycurcumin were the main active components of CP acting on the hepatitis, which were demonstrated to be associated with the inflammatory process that occurs during the progression of hepatitis. Conclusion The protein network module-based approach is an efficient way to investigate the pharmacological mechanisms of CP.

Ethnopharmacological relevance Aconitum carmichaelii Debx. (Fuzi in Chinese) has been widely clinically used to treat heart failure and rheumatism. Whereas its serious toxicity, Radix et Rhizoma Glycyrrhizae (Gancao in Chinese) was combined with it as traditional Chinese medicine (TCM) herb-pair for toxicity reduction and pharmacological effect improvement. Though some previous viewpoints about that has been reported, the underlying interaction mechanism of two herbs remain unknown and definitely worthy of investigating. Aim of study In present study, we focus on Fuzi–Gancao herb-pair precipitation (FGP), considering it related to the compatibility mechanism of Fuzi–Gancao herb-pair. The intestinal absorption and pharmacokinetic characters of 3 diester diterpenoid alkaloids in the precipitation were investigated. Materials and methods Both everted gut sac model and in situ single-pass intestinal perfusion model were used to investigate rat small intestinal permeability and transport mechanism of aconitine, hypaconitine and mesaconitine. Moreover, by means of determination of the plasma concentration, the pharmacokinetic characters of 3 alkaloid compounds in rats have been developed. Results In everted gut sac permeability experiment, the permeability of hypaconitine appeared best in ileum. Furthermore, their uptakes were increased in the presence of P-glycoprotein (P-gp) inhibitors. In situ single-pass intestinal perfusion uptake experiment, results revealed that the transport mechanism may fit the active transport mechanism. And 3 alkaloids in FPG could be absorbed well in rats, fitting 2-compartment model with 1st order absorption and lag time. Conclusions Our results in present study indicated that 3 diester diterpenoid alkaloids in FGP could be dissolved out in gastrointestinal tract firstly and then absorbed in blood after oral administration, which could result in prolonging their mean residence time and adding their absorbed doses, avoiding dose dumping. The current study has significant enlightenments for further investigation on the interaction mechanisms of other acid-base herb-pairs as well as Fuzi–Gancao herb-pair.

Background The effect of chronic stress on cognitive functions has been one of the hot topics in neuroscience. But there has been much controversy over its mechanism. The aim of this study was to investigate the effects of chronic multiple stress on spatial learning and memory as well as the expression of Fyn, BDNF and TrkB in the hippocampus of rats. Methods Adult rats were randomly divided into control and chronic multiple stressed groups. Rats in the multiple stressed group were irregularly and alternatively exposed to situations of vertical revolution, sleep expropriation and restraint lasting for 6 weeks, 6 hours per day with night illumination for 6 weeks. Before and after the period of chronic multiple stresses, the performance of spatial learning and memory of all rats was measured using the Morris Water Maze (MWM). The expression of Fyn, BDNF and TrkB proteins in the hippocampus was assayed by Western blotting and immunohistochemical methods. The levels of Fyn and TrkB mRNAs in the hippocampus of rats were detected by RT-PCR technique. Results The escape latency in the control group and the stressed group were 15.63 and 8.27 seconds respectively. The performance of spatial learning and memory of rats was increased in chronic multiple stressed group (P