System pharmacology analysis to decipher the effect and mechanism of active ingredients combination from Duhuo Jisheng decoction on osteoarthritis in rats.

ETHNOPHARMACOLOGY RELEVANCE: Duhuo Jisheng decoction is a traditional Chinese formula that has been widely used in clinical practice to treat osteoarthritis, which has the effects of removing invaded cold and dampness, relieving joint pain. However, it is difficult to determine the effective substances and mechanisms due to assorted herbs and components, and further research is needed. AIM OF THE STUDY: This study was designed to explore and verify the mechanism and targets of DHJSD in the treatment of OA via network analysis and experiments. METHOD: In this study, the active ingredients of DHJSD were qualitatively analyzed by UPLC-QDA. Network analysis was used to identify common targets and pathways. Next, we explored the therapeutic mechanism of DHJSD through a rat model of knee osteoarthritis. HE staining was used to judge the establishment of the animal model. ELISA and Western blotting were used to verify the expression of key pathway proteins. CONCLUSION: In this study, seventeen chemical constituents in DHJSD were identified. According to the network analysis, we obtained the potential associated pathways of action. Then, molecular docking and SPR experiments showed that the sixteen identified components had high binding energies to IL-6. HE staining showed that the high-dose group of DHJSD had an obvious therapeutic effect on model rats. Compared with the model group, the levels of IL-1ß, TNF-α, IL-6, MMP3, MMP13, ADAMTS4 and ADAMTS5 in serum and the expression of STAT3 and p-STAT3 protein in administration groups were significantly decreased. This result indicated that the IL-6/STAT3 signaling pathway was one of the important pathways regulated by DHJSD to improve OA.

A review of the botany, ethnopharmacology, phytochemistry, analysis method and quality control, processing methods, pharmacological effects, pharmacokinetics and toxicity of codonopsis radix.

Codonopsis Radix, a traditional Chinese medicine in China, has great medicinal and scientific value. Moreover, it can also be used as a health product in daily diet. This paper reviews the botany, ethnopharmacology, phytochemistry, analysis method and quality control, processing methods, pharmacological effects, pharmacokinetics and toxicity related to Codonopsis Radix. The information of Codonopsis Radix is obtained from scientific databases (such as Baidu Scholar, CNKI, Google Scholar, PubMed, Science Direct, Web of Science, and SciFinder Scholar), Chinese herbal classics, Chinese Pharmacopoeia, PhD and MSc dissertations, and so on. The chemical components mainly include alkaloids, alkynes and polyacetylenes, flavonoids, lignans, steroids, terpenoids, organic acids, volatile oils, saccharides and other components, which have a wide range of neuroprotective effects, protection of gastrointestinal mucosa and anti-ulcer, regulation of body immunity, anti-tumor, endocrine regulation, improvement of hematopoietic function, cardiovascular protection, anti-aging and antioxidant effects. In conclusion, this paper summarizes in depth the shortcomings of the current research on Codonopsis Radix and proposes corresponding solutions. At the same time, this paper provides theoretical support for further research on the biological function and potential clinical efficacy of Codonopsis Radix.

Anti-rheumatoid arthritis effects of Xanthii Fructus by affecting the PI3K-AKT signaling pathway based on TMT-labeled quantitative proteomics.

Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic symmetrical multiple arthritis. Current traditional counter-therapies are expensive and have side effects. Xanthii Fructus has effects in expelling wind and cold, draining the nasal orifice, and removing wind and dampness. However, its mechanism of action against rheumatoid arthritis is unknown. In this paper, the mechanism of the anti- rheumatoid arthritis effect of Xanthii Fructus is studied by proteomics. The experimental results show that it could significantly reduce serum inflammatory factor levels, alleviate joint edema, improve vasodilation and congestion, and significantly reduce the number of inflammatory cells. Proteomics results show that the PI3K-AKT signaling pathway is the key pathway for Xanthii Fructus to treat rheumatoid arthritis. In this study, we obtained a new understanding of the mechanism of Xanthii Fructus in the treatment of rheumatoid arthritis, which provided a theoretical basis for its prevention and treatment and laid the foundation for further research.

Systematic review of Lonicerae Japonicae Flos: A significant food and traditional Chinese medicine.

Lonicerae Japonicae Flos has been used as a tea and medicine for more than 1,500 years. It has the functions of clearing heat, detoxification, and is often used to treat carbuncle, furuncle, throat arthralgia, erysipelas, heat-toxic blood dysentery, febrile fever. This paper summarizes the botany, ethnopharmacology, chemical composition and pharmacological action of Lonicerae Japonicae Flos from 1986 to 2022, and looks forward to the future research direction of Lonicerae Japonicae Flos. At present, the components isolated from Lonicerae Japonicae Flos include essential oils, organic acids, flavonoids, iridoids, saponins and other compounds. It has the effects of anti-inflammation, anti-virus, anti-bacteria, anti-oxidation, anti-tumor, protect liver and galltesticles, hypotensive, hypolipidemic, anti-thrombosis, anti-allergy, immune regulation and so on. It is often used in clinical treatment of diarrhea, hematochezia, febrile disease, exogenous wind-heat, and cold, swelling and toxin of carbuncle, sore throat and so on. The comprehensive evaluation of the quality of Lonicerae Japonicae Flos and the understanding of multi-target network pharmacology also need to be studied. As a kind of health food with high value, LJF is worthy of further promotion and development.

Discussion on the molecular mechanism of Duhuo Jisheng decoction in treating osteoarthritis based on network pharmacology and molecular docking.

In this study, network pharmacology and molecular docking technology were used to explore the molecular mechanisms of the Duhuo Jisheng decoction in the treatment of osteoarthritis (OA). The chemical composition of the prescriptions was obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database and the retrieved literature. Targets for the active ingredients were obtained using TCMSP and the Swiss Target Prediction Database. Disease targets were obtained from GeneCards and DisGeNET databases. The online tool, Venny, was used to obtain common targets for drugs and diseases. Protein-protein interactions (PPI) between common targets were analyzed using the search tool for the retrieval of interacting genes/proteins (STRING) database. Common targets were analyzed for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment using the database for annotation, visualization and integrated discovery (DAVID) database. Molecular docking of the first 10 targets and first 10 components was verified using AutoDock Tools software, and the docking diagram was visualized using PyMOL software. After screening, 210 chemical components of the Duhuo Jisheng decoction (DHJSD) were identified. The 253 common targets of drugs and diseases were combined by eliminating repeat values. Based on PPI network analysis, the top ten targets were SRC, STAT3, MAPK3, MAPK1, RELA, PIK3R1, HSP90AA1, TP53, EP300, and AKT1. KEGG analysis showed that DHJSD could regulate the HIF-1, PI3K-Akt, and JAK-STAT signaling pathways. The biological processes involved include inflammatory reactions, the negative regulation of apoptosis, and the positive regulation of cell proliferation. Molecular docking results showed that all targets, except the RELA protein, showed good binding to the compounds, indicating that the 10 components might exert therapeutic effects by binding to the above targets. DHJSD can treat OA by regulating the HIF-1, PI3K-Akt, and JAK-STAT signaling pathways. The proteins involved were SRC, STAT3, MAPK3, MAPK1, and PIK3R1. In this study, network pharmacology was used to predict the mechanism of DHJSD in OA treatment, which was verified by molecular docking to provide experimental research ideas and scientific basis for OA treatment.

Comparison of Pharmacokinetic Profiles of 14 Major Bioactive Components in Normal and Arthritic Model Rats after Oral Administration of Angelicae pubescentis Radix by UPLC-MS/MS.

An ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established to simultaneously determine 14 compounds of Angelicae pubescentis Radix (APR) in normal and arthritis rat plasma in which chloramphenicol and daidzein were used as the internal standards. After protein precipitation with acetonitrile, separation was carried out on a Thermo Hypersil GOLD C18 column using gradient elution with 0.1% formic acid aqueous and acetonitrile consisting as the mobile phase at a flowing rate of 0.3 mL/min. A Thermo TSQ QUANTIS triple quadrupole mass spectrometer was used to detect 14 compounds in positive/negative ion exchange mode and this study was the first to investigate the pharmacokinetic changes of the active compounds in rats under the pathological state of arthritis. The method was verified and the results showed that the intra- and interday precision, accuracy, matrix effect, and extraction recovery were all acceptable, and the analytes were stable under different storage conditions. In addition, the pharmacokinetic behaviors of the 14 compounds were significantly different in model rats compared with normal rats. This indicated that the pharmacokinetic behavior of drugs will vary with the pathological state of the body, which suggested that individualized and reasonable drug administration plans should be formulated for different pathological states in clinical practice. This study provided a scientific basis and data support for better understanding the pharmacodynamic substance basis and clinical application of APR against arthritis.

The effect of anti-alcoholic gastric ulcer before and after vinegar-processed Yuanhu Zhitong prescription based on spectral-effect relationship.

The aim of this study was to screen out the active ingredients of Yuanhu Zhitong prescription (YZP) before and after vinegar processing to play an anti-alcoholic gastric ulcer role through spectrum-effect relationship. First, the fingerprint of 16 batches of YZP was studied using the ultra-high-performance liquid chromatography-quadrupole mass spectrometry detector analysis (UPLC-QDA) method. Second, gastric lesion was induced by anhydrous ethanol. The degree of gastric mucosa injury was evaluated by hematoxylin and eosin staining, and the contents of malondialdehyde and tumor necrosis factor α and superoxide dismutase were detected using the enzyme-linked immunosorbent assay kit. Sixteen batches of YZP were analyzed using the spectrum-effect relationship method. Finally, absorption, distribution, metabolism, and excretion (ADME) was used to evaluate the bioavailability of potential compounds. The results showed that the UPLC-QDA method could successfully establish the fingerprint of YZP. Hematoxylin and eosin staining and biochemical indicators showed that YZP had obvious anti-alcoholic gastric ulcer action. Coptisine chloride, corydaline, berberine chloride, palmatine, imperatorin, and phellopterin were screened out using the spectrum-effect method, and all of them possessed good bioavailability. The results of this study suggest that YZP plays an anti-ulcer role by exerting antioxidant and anti-inflammatory effects through six main active components.

Screening out key compounds of Glechomae Herba for antiurolithic activity and quality control based on spectrum-effect relationships coupled with UPLC-QDA.

Glechomae Herba (GH) has been widely used in the treatment of urolithiasis, especially kidney stones, in China and Southeast Asia. Pharmacological studies have suggested that the antioxidant property of GH contributes to its anticalculus effect. CaSR is one of the main locations of kidney stones, and the mechanism of action of CaSR inhibitors in the treatment of kidney stones is similar to that of GH. However, until now, the antiurolithic chemical compounds in GH and their interaction with CaSR remain unknown. In our study, we revealed the interaction between the active compounds in GH and the active compounds in CaSR inhibitors by using spectrum-effect relationship analysis, pharmacodynamics, and molecular docking techniques. The results showed ten common peaks from the fingerprints of GH extracts from different regions. Pharmacological experiments showed that GH could significantly treat renal tissue lesions. Chlorogenic acid (CA), rosmarinic acid (RA), P5, luteolin, apigenin, and P9 were screened after the analysis of spectrum-effect relationships. In vitro validation experiments showed that all the screened compounds had inhibitory effects on the development of kidney stones in our model. The molecular docking results showed that the above compounds could be docked with CaSR in a natural state, and the docking score was less than 7. This work constructs a general model for the combination of UPLC-QDA and antiurolithic drugs, studies the spectrum-effect relationship of GH, and provides a new possibility for the development of new antiurolithic drugs.

Effect of Xanthii Fructus alcohol extract on proliferation and apoptosis of HFLS-RA and its mechanism.

Xanthii fructus (XF) is the dried and mature fruit of Xanthium sibiricum Patr. It has the effects of anti-inflammatory, antioxidant and anti-arthritic. Rheumatoid arthritis (RA) is the most common inflammatory disorder and often leads to disability. However, there are few studies on the treatment of RA by XF and the specific mechanism of treatment has not been clarified. This study was designed to explore the effects of proliferation and apoptosis by XF on human fibroblast-like synovial-RA (HFLS-RA) cells and investigate its mechanism. The cell proliferation ability was detected by MTS assay. Hoechst 33,342 staining was used to detect apoptosis, and the apoptosis rate was detected by flow cytometry. The expression levels of NF-κB p65 and ß-catenin were detected by Western Blotting. MTS, Hoechst 33,342, flow cytometry analysis showed that the alcohol extract of XF inhibited human fibroblast-like synovial-RA cells proliferation and promoted apoptosis in a dose-dependent manner. Western Blotting experiment showed that the extract of XF could reduce the expression levels of NF-κB p65 and ß-catenin. The extract of XF has a significant therapeutic effect on RA in vitro by regulating NF-κB signaling pathway and Wnt/ß-catenin signaling pathway. Our research will help to clarify the potential pharmacological mechanism of XF on RA and provide experimental basis for the application of XF in clinical treatment.

A Review of the Ethnopharmacology, Phytochemistry, Pharmacology, Application, Quality Control, Processing, Toxicology, and Pharmacokinetics of the Dried Rhizome of Atractylodes macrocephala.

The product investigated herein is the dried rhizome of Atractylodes macrocephala Koidz. [Asteraceae] (Baizhu), which is also known as Dongbaizhu, Wuzhu, Yuzhu, Zhezhu, and Zhongzhu, among others. It invigorates the spleen, replenishes qi, and removes dampness, diuresis, and hidroschesis, and impacts fetal safety. It is often used for the treatment of diseases such as spleen function deficiency, abdominal distension, diarrhea, sputum, vertigo, edema, fever, and sweating and also aids cessation of minimal vaginal bleeding during pregnancy. In this study, research pertaining to the ethnopharmacology, application, phytochemistry, analytical methods, quality control, processing, pharmacology, toxicology, and pharmacokinetics of Baizhu has been reviewed. Relevant information and data reported for Baizhu were collected from CNKI, VIP, PubMed, Web of Science, scientific databases, Chinese Medicinal Material Encyclopedia, Chinese herbal medicine classics, Chinese medicine dictionary, doctoral and master's theses, and so on. Baizhu demonstrates diuretic, antidiuretic, anti-inflammatory effects and antitumor function and aids regulation of gastrointestinal function, hypoglycemic effect, analgesic action, protection on the liver ischemia-reperfusion injury (IRI) in rats, inhibition of aromatase, treatment of bone disease, strengthening myocardial contraction ability, detoxification and cholagogic effect, fall hematic fat action, such as the treatment of acute renal injury, and so on. It also can be an anticoagulant, improve the nervous system disease, affect the immune system, and regulate uterine smooth muscle, antioxidation, antiaging, and antibacterial effect. Sesquiterpenoids, triterpenoids, polyacetylenes, phenylpropanoids, coumarins, flavonoids, flavonoid glycosides, steroids, benzoquinones, polysaccharides, and other compounds were isolated from Baizhu. Among them, sesquiterpenoids, polysaccharides, and polyacetylenes are the main components of Baizhu. Baizhu exhibits a wide range of pharmacological effects and constitutes a considerable proportion of the composition of many proprietary crude drugs. It mainly affects the endocrine, nervous, and urinary systems. The presented information suggests that we should focus on the development of new drugs related to Baizhu, including specific components, to achieve a greater therapeutic potential that can be considered to further explore the information related to Baizhu.

A review of the botany, traditional uses, phytochemistry, and pharmacology of the Flos Inulae.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the genus Inula have long been used as an ethnomedicine in Asia, Europe, and North America for its high medicinal value and health benefits. Inula japonica Thunb. (I. japonica) and Inula britanica L. (I. britanica) are included in Chinese Pharmacopoeia (2020 edition) as the traditional Chinese medicine Flos inulae (FI). In TCM, FI tastes bitter, pungent, and salt, with warm nature and has the functions of water removal, reduction in nausea, and prevention of vomiting and is often used for cold-related coughs, sputum, wheezing coughs, vomiting, belching and other related diseases. In addition, Inula japonica Thunb is used as a botanical medicine in Korea and Inula britannica L. is also used as a traditional plant medicine in Iran. AIM OF THE STUDY: This paper collects the relevant research literature (1970-2021) and provides a systematic summary of the botany, ethnopharmacology, processing, phytochemistry, pharmacology, toxicity, analytical methods and quality control of FI to explore its potential and expand its scope for better clinical application. MATERIALS AND METHODS: Information on Inula japonica Thunb. and Inula britanica L. was collected from scientific databases (1970-2021), including Google Scholar, Baidu Scholar, Springer, PubMed, CNKI and Wan Fang DATA. Information was also collected from classic books of Chinese herbal medicine and Ph.D. and M.Sc. theses. RESULTS: More than 200 chemical compounds have been isolated from Inula japonica Thunb. and Inula britanica L., including sesquiterpenes, flavonoids, volatile oils, triterpenoids, diterpenoid glycosides, monoterpenoids, polysaccharides, steroid and small molecule acids. Based on a wide variety of chemically active ingredients, FI has a wide range of pharmacological effects. Modern pharmacological research has proven that the pharmacological effects of FI include anti-inflammatory, antitumor, antioxidant, antiallergy, antidiabetic, blood lipid reduction, skin whitening, liver protection, anticonstipation, and antinociceptive effects. CONCLUSIONS: FI is a very important traditional Chinese herbal medicine with anti-inflammatory antitumor, antioxidant, antiallergy, antidiabetic and other pharmacological effects that can treat a variety of related diseases. This paper summarizes the botany, ethnopharmacology, processing, phytochemistry, pharmacology, toxicity, analytical methods, and quality control of FI. However, the research on the processing, toxicity and quality control of FI is currently too shallow, especially concerning the relationship between the changes in active components before and after processing and the changes in its pharmacological action, which remains unclear. There are few toxicity experiments conducted with FI, so it is impossible to evaluate the safety of FI objectively and impartially. There are also few studies on the material basis and doses of FI causing toxicity and side effects, and more in-depth and concrete researches should be carried out in the future regarding these aspects. Furthermore, to ensure effective and safe clinical medication, we should also pay attention to the mixed use of FI in various regions of China to control the quality of the FI plant.

A review: the botany, ethnopharmacology, phytochemistry, pharmacology of Cinnamomi cortex.

Cinnamomi Cortex (CC) is the dried bark of Cinnamomum cassia (L.) J. Presl. Modern pharmacological research shows that CC can be used to treat diabetes, breast cancer, leukemia and other diseases. It has been used for more than 2000 years in China, mainly distributed in Guangxi, Guangdong, Yunnan and Fujian. In this paper, the botany, ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and other aspects of CC are summarized. We hope to provide convenience for the further exploration and development of CC. There are more than 300 components isolated from CC including essential oils, polyphenols, diterpenes and sesquiterpenes, flavonoids, polysaccharides and others. Pharmacological studies show that CC has a wide range of pharmacological activities such as anti-inflammatory, antibacterial, antioxidant, antitumor, improving glucose and lipid metabolism, neuroprotection and so on. It shows that CC has great potential to develop into a cheap, low-toxicity and highly-efficient natural therapeutic drug. However, there is still a long way to go for research of CC, although great progress has been made. For instance, clinical practices for CC recorded in traditional medicine books need to be paid more attention. Present achievements are still not enough to clearly explain the mechanism for some diseases. New skeletons and new drugs will be required to be discovered, so that the potential of CC can be brought into full play.

The phytochemistry, pharmacology and traditional medicinal use of Glechomae Herba - a systematic review.

Glechomae Herba is a Chinese herb, which has been used in China for thousands of years, mainly for the treatment of nephrolithiasis. This paper summarizes the modern research progress on Glechomae Herba from the aspects of botany, traditional medicinal use, phytochemistry, pharmacology, pharmacokinetics, analytical methods and quality control. In addition, it also points out the deficiencies of current research on this herb and provides possible directions for its development. So far, more than 190 chemical components have been isolated and identified from Glechomae Herba, including organic acids and their esters, volatile oils, flavonoids and their glycosides, terpenes and other chemical components. Its extracts and compounds have a wide range of pharmacological effects, including anti-stone, anti-inflammatory, bacteriostatic, cholagogic and diuretic, effect on ileum smooth muscle, anti-tumor effect on tumor and hypoglycemic effects. However, future studies should focus on drug metabolism, clarify its pharmacodynamic mechanism, and establish a reasonable quality control standards for Glechomae Herba.

Panacis Quinquefolii Radix: A Review of the Botany, Phytochemistry, Quality Control, Pharmacology, Toxicology and Industrial Applications Research Progress.

On January 2, 2020, The National Health Commission and the State Administration for Market Regulation listed Panacis Quinquefolii Radix (PQR) as a medicinal and food homologous product. PQR is the dry root of Panax quinquefolium L., which has the functions of replenishing qi and nourishing Yin, clearing heat and producing body fluid. It is often used for qi deficiency and Yin deficiency, heat exhaustion, asthma and phlegm, dry mouth and pharynx. PQR is sweet, slightly bitter and cool in nature, and enter the heart, lung and kidney meridian exerts the remedial and hygienical effect. At present, active components such as saponins, flavonoids, fatty acids, polyalkynes, volatile oils and other nutrients such as amino acids, carbohydrates, vitamins and trace elements have been isolated from PQR. Modern pharmacological studies have shown that PQR has the effects of hypoglycemic, antihypertensive, anti fatigue, anti-oxidation, anti-tumor, immunomodulatory, neuroprotective and so on. In addition, PQR is recognized as a health care product to strengthen the body and dispel diseases. It is not only the raw material of Traditional Chinese medicine preparations, but also the treasure of dietary therapy and herbal cuisine. This study not only reviewed the botany, phytochemistry and pharmacology of PQR, but also summarized its quality control, toxicity and industrial applications for the first time. This paper not only summarizes the development status of PQR, but also analyzes the shortcomings of the current research on PQR, and puts forward the corresponding solutions, in order to provide reference for future scholars to study PQR.

Botany, traditional uses, phytochemistry, analytical methods, processing, pharmacology and pharmacokinetics of Bupleuri Radix: A systematic review.

Bupleuri Radix (BR) is the dry root of Bupleurum chinense DC. and Bupleurum scorzonerifolium Willd. It has the functions of evacuation and antipyretic, soothing liver and relieving depression and often used to treat cold fever, chest and rib swelling pain, irregular menstruation, uterine prolapse, rectocele and other diseases. In this paper, the botany, traditional application, phytochemistry, pharmacology and toxicity of BR were reviewed. On the basis of limited literature, the analytical method, quality control, processing method, processing effect and pharmacokinetics of BR were summarized and analyzed for the first time. This review makes an in-depth discussion on the shortcomings of the current research on BR, and puts forward its own views and solutions. This has never been summarized in the previous review of BR. It is of great practical significance for future scholars to find a breakthrough point in the study of BR. So far, its mechanism has not been satisfactorily explained. Moreover, the comprehensive quality evaluation and multi-target network pharmacology of BR need to be further studied. In the future, more in vitro and in vivo experiments are needed to give full play to the therapeutic potential of BR.