Hydroxy-α-sanshool from the fruits of Zanthoxylum bungeanum Maxim. promotes browning of white fat by activating TRPV1 to induce PPAR-γ deacetylation.

BACKGROUND: Accumulating evidence suggested increasing energy expenditure is a feasible strategy for combating obesity, and browning of white adipose tissue (WAT) to promote thermogenesis might be one of the attractive ways. Hydroxy-α-sanshool (HAS), a natural amide alkaloid extracted from the fruits of Zanthoxylum bungeanum Maxim, possesses lots of benefits in lipid metabolism regulation. METHODS: The anti-obesity effect of HAS was investigated by establishing an animal model of obesity and a 3T3-L1 differentiation cell model. Effects of HAS on the whole-body fat and liver of obese mice, and the role of HAS in inducing browning of white fat were studied by Micro CT, Metabolic cage detection, Cell mitochondrial pressure detection, transmission electron microscopy and cold exposure assays. Furthermore, the Real-time PCR (qPCR), digital PCR (dPCR), western blot, Co-immunoprecipitation (Co-IP), molecular docking, drug affinity responsive target stability (DARTS), Cellular thermal shift assay (CETSA) and other methods were used to investigate the target and mechanisms of HAS. RESULTS: We found that treatment with HAS helped mice combat obesity caused by a high fat diet (HFD) and improve metabolic characteristics. In addition, our results suggested that the anti-obesity effect of HAS is related to increase energy consumption and thermogenesis via induction of browning of WAT. The further investigations uncovered that HAS can up-regulate UCP-1 expression, increase mitochondria number, and elevate the cellular oxygen consumption rates (OCRs) of white adipocytes. Importantly, the results indicated that browning effects of HAS is closely associated with SIRT1-dependent PPAR-γ deacetylation through activating the TRPV1/AMPK pathway, and TRPV1 is the potential drug target of HAS for the browning effects of WAT. CONCLUSIONS: Our results suggested the HAS can promote browning of WAT via regulating AMPK/SIRT-1/PPARγ signaling, and the potential drug target of HAS is the membrane receptor of TRPV1.

Targeting TRPV1 and TRPA1: A feasible strategy for natural herbal medicines to combat postoperative ileus.

Under physiological or pathological conditions, transient receptor potential (TRP) channel vanilloid type 1 (TRPV1) and TRP ankyrin 1 (TRPA1) possess the ability to detect a vast array of stimuli and execute diverse functions. Interestingly, increasing works have reported that activation of TRPV1 and TRPA1 could also be beneficial for ameliorating postoperative ileus (POI). Increasing research has revealed that the gastrointestinal (GI) tract is rich in TRPV1/TRPA1, which can be stimulated by capsaicin, allicin and other compounds. This activation stimulates a variety of neurotransmitters, leading to increased intestinal motility and providing protective effects against GI injury. POI is the most common emergent complication following abdominal and pelvic surgery, and is characterized by postoperative bowel dysfunction, pain, and inflammatory responses. It is noteworthy that natural herbs are gradually gaining recognition as a potential therapeutic option for POI due to the lack of effective pharmacological interventions. Therefore, the focus of this paper is on the TRPV1/TRPA1 channel, and an analysis and summary of the processes and mechanism by which natural herbs activate TRPV1/TRPA1 to enhance GI motility and relieve pain are provided, which will lay the foundation for the development of natural herb treatments for this disease.

Hydroxy-α-sanshool isolated from Zanthoxylum bungeanum Maxim. has antidiabetic effects on high-fat-fed and streptozotocin-treated mice via increasing glycogen synthesis by regulation of PI3K/Akt/GSK-3ß/GS signaling.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by hyperglycemia. The fruits of Zanthoxylum bungeanum Maxim. is a common spice and herbal medicine in China, and hydroxy-α-sanshool (HAS) is the most abundant amide in Z. bungeanum and reported to have significant hypoglycemic effects. The purpose of this study was to evaluate the ameliorative effects of HAS on T2DM and the potential mechanisms responsible for those effects. An acute toxicity test revealed the median lethal dose (LD50) of HAS is 73 mg/kg. C57BL/6 J mice were fed a high-fat diet and given an intraperitoneal injection of streptozotocin (STZ) to induce T2DM in mice to evaluate the hypoglycemic effects of HAS. The results showed that HAS significantly reduced fasting blood glucose, reduced pathological changes in the liver and pancreas, and increased liver glycogen content. In addition, glucosamine (GlcN)-induced HepG2 cells were used to establish an insulin resistance cell model and explore the molecular mechanisms of HAS activity. The results demonstrated that HAS significantly increases glucose uptake and glycogen synthesis in HepG2 cells and activates the PI3K/Akt pathway in GlcN-induced cells, as well as increases GSK-3ß phosphorylation, suppresses phosphorylation of glycogen synthase (GS) and increases glycogen synthesis in liver cells. Furthermore, these effects of HAS were blocked by the PI3K inhibitor LY294002. The results of our study suggest that HAS reduces hepatic insulin resistance and increases hepatic glycogen synthesis by activating the PI3K/Akt/GSK-3ß/GS signaling pathway.

Targeting matrix metalloproteases: A promising strategy for herbal medicines to treat rheumatoid arthritis.

As a type of metalloproteinase, matrix metalloproteinases (MMPs) can be divided into collagenase, gelatinase, stromelysins, membrane-type (MT)-MMPs and heterogeneous subgroups according to their structure and function. MMP contents in the human body are strictly regulated, and their synthesis, activation and inhibition processes should be kept in a certain balance; otherwise, this would result in the occurrence of various diseases. Rheumatoid arthritis (RA) is a known immune-mediated systemic inflammatory disease that is affected by a variety of endogenous and exogenous factors. In RA development, MMPs act as important mediators of inflammation and participate in the degradation of extracellular matrix substrates and digestion of fibrillar collagens, leading to the destruction of joint structures. Interestingly, increasing evidence has suggested that herbal medicines have many advantages in RA due to their multitarget properties. In this paper, literature was obtained through electronic databases, including the Web of Science, PubMed, Google Scholar, Springer, and CNKI (Chinese). After classification and analysis, herbal medicines were found to inhibit the inflammatory process of RA by regulating MMPs and protecting joint structures. However, further preclinical and clinical studies are needed to support this view before these herbal medicines can be developed into drugs with actual application to the disease.

Fructus Zanthoxyli extract improves glycolipid metabolism disorder of type 2 diabetes mellitus via activation of AMPK/PI3K/Akt pathway: Network pharmacology and experimental validation.

OBJECTIVE: This study investigated the potential mechanisms behind the beneficial effects of Fructus Zanthoxyli (FZ) against type 2 diabetes mellitus (T2DM) based on network pharmacology and experimental validation. METHODS: Ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry, and gas chromatography-mass spectrometry were used to identify the constituents of FZ. Next, the differentially expressed genes linked to the treatment of diabetes with FZ were screened using online databases (including Gene Expression Omnibus database and Swiss Target Prediction online database), and the overlapping genes and their enrichment were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the pathway was verified by in vitro experiments, and cell staining with oil red and Nile red showed that the extract of FZ had a therapeutic effect on T2DM. RESULTS: A total of 43 components were identified from FZ, and 39 differentially expressed overlapping genes were screened as the possible targets of FZ in T2DM. The dug component-target network indicated that PPARA, PPARG, PIK3R3, JAK2 and GPR88 might be the core genes targeted by FZ in the treatment of T2DM. Interestingly, the enrichment analysis of KEGG showed that effects of FZ against T2DM were closely correlated with the adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathways. In vitro experiments further confirmed that FZ significantly inhibited palmitic acid-induced lipid formation in HepG2 cells. Moreover, FZ treatment was able to promote the AMPK and PI3K/Akt expressions in HepG2 cells. CONCLUSION: Network pharmacology combined with experimental validation revealed that FZ extract can improve the glycolipid metabolism disorder of T2DM via activation of the AMPK/PI3K/Akt pathway.

Glabridin from Glycyrrhiza glabra Possesses a Therapeutic Role against Keloid via Attenuating PI3K/Akt and Transforming Growth Factor-ß1/SMAD Signaling Pathways.

Glabridin (Gla) is a typical flavonoid isolated from the Glycyrrhiza glabra with various bioactivities and is a common additive in many cosmetics. In our study, we evaluated the antiscarring effect of Gla from G. glabra in a rabbit ear hyperplastic scar model. Hematoxylin and eosin staining and Masson staining were applied to determine the pathological changes and collagen fibers of scar tissue in rabbits. The results suggested that Gla could reduce rabbit ear scar hyperplasia, inhibit inflammation, and decrease collagen production. Furthermore, the in vitro cell experiments were applied to determine the effects of Gla on human keloid fibroblasts (HKFs), and we observed that Gla suppressed the HKF cells' proliferation via inducing apoptosis. Subsequently, we found that Gla reduced collagen production in HKF cells. The further molecular mechanisms investigations suggested that Gla played a therapeutic role against keloid by attenuating PI3K/Akt and TGFß1/SMAD pathways. Our study would be beneficial for extending the applications of the known sweet plant of G. glabra.

Discovery of Active Ingredients in Traditional Chinese Medicine Based on the Analysis of Odor and Flavor of Compounds.

BACKGROUND: The odor and flavor produced by a complex mixture of chemical components with different amounts and thresholds constitute a unique property for food and Traditional Chinese Medicine (TCM). These compounds usually belong to mono- and sesquiterpenes, esters, lipids, and others. OBJECTIVE: This review aimed to demonstrate the extraction method and reliable technology for identifying the compounds responsible for their odor and flavor. METHODS: Existing techniques have been summarized for the analysis of taste and odor components and their characteristics, such as electronic nose (enose, EN) and electronic tongue (etongue, ET), which can separate high-quality food from low-quality and natural from artificial food in terms of unique odor and flavor. RESULTS: Gas chromatography-olfactometry mass spectrometry (GC-O-MS), a technique derived from Gas chromatography mass spectrometry (GC-MS), coupled with human sense by Olfactory Detector Ports has been successfully applied for screening of the odor-producing components for the food or Chinese medicine. CONCLUSION: This current review provides some guidelines for quality evaluation of food or Chinese medicine.

Effects of Musk Volatile Compounds on Attenuated Nerve Injury and Improving Post-cerebral Ischemic Exercise Functions.

BACKGROUND: Reperfusion Injury Acute ischemic stroke is increasing in people recently and Musk, as a commonly used Traditional Chinese Medicine (TCM), has been suggested as a potential agent against acute ischemic stroke, but the efficacies and underlying mechanisms of it remain unknown. OBJECTIVE: This study was aimed to test the hypotheses that volatile compounds of musk could attenuate nerve injury and identify the bioactive compounds and potential mechanisms of Musk. METHODS: Transient middle cerebral artery occlusion (MCAO) model in vivo in Sprague-Dawley rats (SD rats) was used to test this hypothesis. Collecting ingredients of Musk and their related targets were discerned from the Gas chromatography-olfactory mass spectrometry (GC-O-MS) experiment. Then the potential mechanisms and targets of the compounds were searched by network pharmacology techniques. Finally, the pathway was verified by Western Bolt (WB). RESULTS: First, Musk treatment significantly up-regulated the relative levels of AKT1, PI3KA, and VEGFA in the hippocampus, and improved the sport functions in the post-MCAO ischemic rats in vivo. Next, twenty potential flavor active compounds were recognized by GC-O-MS. A total of 89 key targets including HIF-1, PIK3CA, TNF signaling pathway, and VEGF were identified. AKT1, HIF1A, PIK3CA, and VEGFA were viewed as the most important genes, which were validated by molecular docking simulation. CONCLUSION: The Volatile compounds of musk can attenuate nerve injury and improving post-cerebral ischemic exercise functions by HIF1A pathways, and the combined data provide novel insight for Musk volatile compounds developed as new drug for improving reperfusion injury in acute ischemic stroke.

Phytochemicals in traditional Chinese medicine can treat gout by regulating intestinal flora through inactivating NLRP3 and inhibiting XOD activity.

OBJECTIVES: Gout is a common disease caused by hyperglycemia. Traditional drugs for gout have both good therapeutic effects and serious side effects. Traditional Chinese medicine (TCM) is one of the potential sources of modern medicine, and is the development of new drugs for many diseases, including gout. TCM is an indispensable part of gout treatment. Compared with anti-gout medication commonly used in clinic (e.g. the xanthine oxidase inhibitors allopurinol and febuxostat), traditional Chinese medicine has fewer side effects in the treatment of gout and can safely control serum uric acid and the level of inflammation. However, there have been few studies on how traditional Chinese medicine controls uric acid and inflammation levels in patients with gout. KEY FINDINGS: Herbs are a valuable resource in the search for new drugs to treat many diseases, including gout. Phytochemicals in TCM treatment of gout mainly includes two aspects, anti-inflammatory and reducing uric acid content. The anti-inflammatory mechanism is mainly through the inactivation of NF-κB and NLRP3 inflammasome to reduce the inflammatory response induced by uric acid crystals. The mechanism of lowering uric acid is mainly through inhibiting the activity of xanthine oxidase and up-regulating the expression of URAT1 and GLUT9.In recent years, the intestinal flora has become a new field of understanding diseases. It has been observed that the occurrence of gout is closely related to changes in the intestinal flora. Herbaceous plants contain fiber, polyphenols, polysaccharides and other active components. When taken orally, Chinese herbs act like prebiotics. After traditional Chinese medicine treatment, the abundance levels of Bifidobacterium, Lactobacillus, Bacteroidetes and Prevotella were increased, while the abundance of Proteus and the Firmicutes/Bacteroidetes ratio were decreased. Changes in the intestinal flora led to further changes in its metabolites, including short-chain fatty acids (SCFAs) and lipopolysaccharide (LPS), which ultimately down-regulate the TLR4/NF-κB inflammatory signaling pathway, up-regulate GLUT9 and URAT1 gene expression and inhibition of xanthine oxidase activity. Destruction of the intestinal barrier is also an important factor in the occurrence of gout. Disruption of the intestinal barrier allows LPS to enter the bloodstream and activates the expression of various inflammatory factors, which causes gout.

Natural substances derived from herbs or plants are promising sources of anticancer agents against colorectal cancer via triggering apoptosis.

OBJECTIVES: Nowadays, one of the most common gastrointestinal cancers is colorectal cancer (CRC). Chemotherapy is still one of the main methods to treat cancer. However, the currently available synthetic chemotherapy drugs often cause serious adverse reactions. Apoptosis is generally considered as an ideal way for induction the death of tumour cells without the body's inflammatory response, and it is reported that lots of natural agents could trigger various cancer cells to apoptosis. The overarching aim of this project was to elucidate the specific mechanisms by which natural substances induce apoptosis in CRC cells and to be used as an alternative therapeutic option in the future. KEY FINDINGS: The mechanisms for the pro-apoptotic effects of natural substances derived from herbs or plants include death receptor pathway, mitochondrial pathway, endoplasmic reticulum stress pathway, related signal transduction pathways (PI3K/Akt, MAPK, p53 signalling), and so on. SUMMARY: This paper updated this information regarding the anti-tumour effects of natural agents via induction of apoptosis against CRC, which would be beneficial for future new drug research regarding natural products from herbs or plants.

Current strategies and technologies for finding drug targets of active components from traditional Chinese medicine.

Introduction: The ambiguity of the drug target is one of the major factors restricting the development of traditional Chinese medicine (TCMs) and its bioactive constituents. The characteristics of "multiple components, multiple targets and multiple pathways" of TCMs make the research of drug targets extremely difficult. With the emergence of new theories, there are increasing technologies and strategies that can be used for the drug targets research of TCMs. In this paper, we summarize several techniques and methods applied to the study of TCM targets. Methods: Through consulting a large number of literature, research and summary, and finally summarized the application direction of the technical method, advantages and limitations. Results: The methods and techniques including computer aided drug design, network pharmacology, phage display, affinity fishing, drug affinity responsive target stability and cellular thermal shift assay were summarized, and their application directions, advantages and disadvantages were discussed. At the same time, a large number of application examples were given to provide reference for the research of TCM targets.

Antiepileptic Effects of Cicadae Periostracum on Mice and Its Antiapoptotic Effects in H2O2-Stimulated PC12 Cells via Regulation of PI3K/Akt/Nrf2 Signaling Pathways.

Cicadae Periostracum (CPM), a commonly used animal traditional Chinese medicine (TCM), possesses antifebrile, spasmolytic, antiasthmatic, and antiphlogistic effects. In our present paper, we aimed to systemically investigate the antiepileptic effects of CPM in epileptic mice and explore the related molecular mechanism. Pentylenetetrazole- (PTZ) and strychnine-induced convulsion mice were established, and the results showed CPM could prolong the latency of convulsion and death and improve the neuronal damage in the hippocampus of PTZ-induced mice. Furthermore, the H2O2-treated PC12 cells were prepared to explore the possible mechanisms for the antiepileptic effects of CPM. CCK-8 results showed that CPM significantly improved the cell viability of H2O2-treated PC12 cells. Results of the acridine orange- (AO-) ethidium bromide (EB) staining, cell mitochondrial membrane potential (MOMP) analysis, and flow cytometry analysis showed that CPM significantly suppressed the H2O2-induced apoptosis in PC12 cells. In addition, CPM also downregulated the proapoptosis proteins, including Bax, cleaved- (C-) caspase-3, and C-caspase-9, and upregulated Bcl-2. Furthermore, CPM reduced the reactive oxygen species (ROS) levels via increasing antioxidative enzyme activities, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Importantly, CPM could increase the phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) in H2O2-induced PC12 cells and can promote the nuclear transfer of the nuclear factor E2-related factor 2 (Nrf2) and increase the expression of heme oxygenase-1 (HO-1) in the cytoplasm. In conclusion, our present study suggested CPM possessed antiepileptic effects through antiapoptosis of neuron cells via regulation of the PI3K/Akt/Nrf2 signaling pathway.

Research progress regarding potential effects of traditional Chinese medicine on postoperative intestinal obstruction.

OBJECTIVES: Postoperative intestinal obstruction is a common postoperative complication with typical symptoms of abdominal pain, vomiting, abdominal distension and constipation. The principal aim of this paper is to provide a full-scale review on the categories and characteristics of postoperative intestinal obstruction, pathophysiology, effects and detailed mechanisms of compounds and monomers from traditional Chinese medicine for treating postoperative intestinal obstruction. Moreover, the possible development and perspectives for future research are also analyzed. METHODS: Literature regarding postoperative intestinal obstruction as well as the anti-pio effect of aqueous extracts and monomers from traditional Chinese medicine in the last 20 years was summarized. KEY FINDINGS: To date, approximately 30 compounds and 25 monomers isolated from traditional Chinese medicine including terpenes, alkaloids, polysaccharides, flavonoids, phenylpropanoids and quinones, have exerted significant antipio effect. This paper reviews the effective doses, models, detailed mechanisms, and composition of these traditional Chinese medicine compounds, as well as the structure of these monomers. Moreover, challenges existed in the current investigation and further perspectives were discussed as well, hoping to provide a reference for future clinical treatment of postoperative intestinal obstruction and the development of new drugs. CONCLUSIONS: Above all, the convincing evidence from modern pharmacology studies powerfully supported the great potential of traditional Chinese medicine in the management of postoperative intestinal obstruction. Regrettably, less attention was currently paid on the mechanisms of traditional Chinese medicine compounds and monomers with antipio effect. Consequently, future study should focus on monomer-mechanism and structure-function relationship.

Identification of the active substances and mechanisms of ginger for the treatment of colon cancer based on network pharmacology and molecular docking.

BACKGROUND AND OBJECTIVE: Colon cancer is occurring at an increasing rate and ginger (Zingiber officinale), as a commonly used herbal medicine, has been suggested as a potential agent for colon cancer. This study was aimed to identify the bioactive components and potential mechanisms of ginger for colon cancer prevention by an integrated network pharmacology approach. METHODS: The putative ingredients of ginger and its related targets were discerned from the TCMSP  and Swiss target prediction database. After that, the targets interacting with colon cancer were collected using Genecards, OMIM, and Drugbank databases. KEGG pathway and GO enrichment analysis were performed to explore the signaling pathways related to ginger for colon cancer treatments. The PPI and compound-target-disease networks were constructed using Cytoscape 3.8.1. Finally, Discovery studio software was employed to confirm the key genes and active components from ginger. RESULTS: Six potential active compounds, 285 interacting targets in addition to 1356 disease-related targets were collected, of which 118 intersection targets were obtained. A total of 34 key targets including PIK3CA, SRC, and TP53 were identified through PPI network analysis. These targets were mainly focused on the biological processes of phosphatidylinositol 3-kinase signaling, cellular response to oxidative stress, and cellular response to peptide hormone stimulus. The KEGG enrichment manifested that three signaling pathways were closely related to colon cancer prevention of ginger, cancer, endocrine resistance, and hepatitis B pathways. TP53, HSP90AA1, and JAK2 were viewed as the most important genes, which were validated by molecular docking simulation. CONCLUSION: This study demonstrated that ginger produced preventive effects against colon cancer by regulating multi-targets and multi-pathways with multi-components. And, the combined data provide novel insight for ginger compounds developed as new drug for anti-colon cancer.

Network Pharmacology and Molecular Docking Approaches to Investigating the Mechanism of Action of Zanthoxylum bungeanum in the Treatment of Oxidative Stress-induced Diseases.

BACKGROUND: Zanthoxylum bungeanum Maxim., a traditional Chinese herbal medicine, has been reported to possess therapeutic effects on diseases induced by oxidative stress (DOS), such as atherosclerosis and diabetes complication. However, the active components and their related mechanisms are still not systematically reported. OBJECTIVE: The current study was aimed to explore the main active ingredients and their molecular mechanisms of Z. bungeanum for treating DOS using network pharmacology combined with molecular docking simulation. METHODS: The active components of Z. bungeanum pericarps, in addition to the interacting targets, were identified from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. These components were filtered using the parameters of oral bioavailability and drug-likeness, and the targets related to DOS were obtained from the Genecards and OMIM database. Furthermore, the overlapping genes were obtained, and a protein-protein interaction was visualized using the STRING database. Next, the Cytoscape software was employed to build a disease/drug/component/target network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using R software. Finally, the potential active compounds and their related targets were validated using molecular docking technology. RESULTS: A total of 61 active compounds, 280 intersection genes, and 105 signaling pathways were obtained. Functional enrichment analysis suggested that DOS occurs possibly through the regulation of many biological pathways, such as AGE-RAGE and HIF-1 signaling pathways. Thirty of the identical target genes showed obvious compact relationships with others in the STRING analysis. Three active compounds, quercetin, diosmetin, and beta-sitosterol, interacting with the four key targets, exhibited strong affinities. CONCLUSION: The findings of this study not only indicate the main mechanisms involving in oxidative stress-induced diseases but also provide the basis for further research on the active components of Z. bungeanum for treating DOS.

Processing methods and mechanisms for alkaloid-rich Chinese herbal medicines: A review.

The processing of Chinese herbal medicine is a form of pharmaceutical technology developed over thousands of years, in order to increase efficiency and decrease toxicity of herbs in traditional Chinese medicine (TCM). Herbal processing is essential for safe and effective application of TCM in clinical practice, as it alters the active chemical components and therefore the functions of herbal medicines. Alkaloid-rich herbal medicines in TCM are commonly processed by cleansing, cutting, processing by dry stir-frying, stir-frying with liquid adjuvants, and processing by water decoction. In addition, commonly used adjuvants for processing alkaloid-rich herbal medicines are river sand, wine, vinegar, brine, honey and herbal juice. For alkaloid-rich herbal medicines, the main chemical reactions that occur during processing include hydrolysis, oxidation, replacement, decomposition and condensation. This paper aimed to summarize the processing methods and mechanisms for alkaloid-rich Chinese herbal medicines, and provide much-needed theoretical support and scientific evidence for understanding those mechanisms and effects. Information on processing methods for alkaloid-rich herbal medicines was collected from classic books of herbal medicine, PhD and MSc dissertations, online scientific databases including PubMed, SciFinder, Scopus, Web of Science, Baidu Scholar and Google Scholar. This paper should help to advance our knowledge of the processing mechanisms and aid in the development of processing methods for alkaloid-rich Chinese herbal medicines.

HIF-1α is a Potential Molecular Target for Herbal Medicine to Treat Diseases.

HIF-1α is an important factor regulating oxygen balance in mammals, and its expression is closely related to various physiological and pathological conditions of the body. Because HIF-1α plays an important role in the occurrence and development of cancer and other diseases, it has become an enduring research hotspot. At the same time, natural medicines and traditional Chinese medicine compounds have amazing curative effects in various diseases related to HIF-1 subtype due to their unique pharmacological effects and more effective ingredients. Therefore, in this article, we first outline the structure of HIF-1α and the regulation related to its expression, then introduce various diseases closely related to HIF-1α, and finally focus on the regulation of natural medicines and compound Chinese medicines through various pathways. This will help us understand HIF-1α systematically, and use HIF-1α as a target to discover more natural medicines and traditional Chinese medicines that can treat related diseases.

Anti-proliferation and anti-migration effects of an aqueous extract of Cinnamomi ramulus on MH7A rheumatoid arthritis-derived fibroblast-like synoviocytes through induction of apoptosis, cell arrest and suppression of matrix metalloproteinase.

CONTEXT: Cinnamomi ramulus, the dry twig of Cinnamomum cassia Presl. (Lauraceae), has been reported to exert several activities such as antitumor, anti-inflammatory, and analgesic effects. OBJECTIVE: This study investigates the effects of an aqueous extract of Cinnamomi ramulus (ACR) on rheumatoid arthritis (RA). MATERIALS AND METHODS: TNF-α-induced RA-derived fibroblast-like synoviocyte MH7A cells were incubated with ACR (0.1-2 mg/mL) for 24 h. The proliferation was tested using CCK-8 and colony formation assays. The migration and invasion abilities were measured using transwell tests and wound healing assays. Apoptosis and cell cycle were examined by flow cytometry. The potential mechanisms were determined by western blotting and quantitative real-time PCR. UPLC-QE-MS/MS was used for chromatographic analysis of ACR and its compounds were identified. Molecular docking strategy was used to screen the potential anti-RA active compounds of ACR. RESULTS: We found that ACR induced apoptosis in MH7A cells at concentrations of 0.4, 0.8, and 1.2 mg/mL. The proliferation of MH7A cells was reduced and the cell cycle was blocked in the G2/M phase at concentrations of 0.2, 0.4, 0.6 mg/mL. Migration and invasion of MH7A cells were reduced through inhibiting the expression of MMP-1, MMP-2, and MMP-3. The molecular docking strategy results showed that 9 compounds in ACR have good affinity with protein crystal, and benzyl cinnamate (10-100 µg/mL) could inhibit cell migration and induce apoptosis. CONCLUSIONS: The anti-RA effect of ACR may be attributed to its anti-proliferative and anti-migration effects on synovial fibroblasts. These data suggest that Cinnamomi ramulus may have therapeutic value for the treatment of RA.

Botanical and Traditional Uses and Phytochemical, Pharmacological, Pharmacokinetic, and Toxicological Characteristics of Ziziphi Spinosae Semen: A Review.

Ziziphi Spinosae Semen (ZS, the seeds of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou) is used as a traditional Chinese medicine referred to as Suan zao ren (). This paper aims to provide a systematic review of its traditional uses and its botanical, phytochemical, pharmacological, pharmacokinetic, and toxicological characteristics. The future development and research prospects for ZS have also been discussed in detail. To date, over 150 compounds have been identified in this plant, including terpenoids, alkaloids, flavonoids, fatty acids, volatile oils, polysaccharides, and others. Both extracts and purified compounds have excellent biological activities, especially sedative and hypnotic effects. Other effects include ameliorating effect of learning and memory, anti-inflammation, antioxidation, blood pressure and lipid lowering, antiaging, and antitumor effects. Thus, this traditional Chinese medicine can be used to treat many diseases such as insomnia, forgetfulness, headaches, and dizziness. Although many of the traditional uses of ZS are well established, the relationship between structure and function still needs to be further studied. In order to better pave the way for research and the establishment of quality control standards for ZS, it will be very important to elucidate its pharmacological mechanisms of action and explore new clinical effects.

Hydroxy-α-sanshool Possesses Protective Potentials on H2O2-Stimulated PC12 Cells by Suppression of Oxidative Stress-Induced Apoptosis through Regulation of PI3K/Akt Signal Pathway.

Zanthoxylum bungeanum pericarp is a commonly used herbal medicine in China with effects of anti-inflammatory and analgesic, improving learning and memory ability, while hydroxy-α-sanshool (HAS) is the most important active ingredient of Z. bungeanum pericarps. The purpose of this study was to investigate the neuroprotective effect of HAS and its related possible mechanisms using a H2O2-stimulated PC12 cell model. CCK-8 assay results showed that HAS had a significant protective effect on H2O2-stimulated PC12 cells without obvious cytotoxicity on normal PC12 cells. Flow cytometry and fluorescence microscope (DAPI staining and DCFH-DA staining) indicated that HAS could reduce the H2O2-induced apoptosis in PC12 cells via reduction of intracellular ROS and increase of mitochondrial membrane potential (MMP). Subsequently, results of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) determination suggested that HAS could increase the enzyme activities of SOD, CAT, and GSH-Px whereas it could decrease the MDA contents in H2O2-stimulated PC12 cells. Furthermore, the western blotting assays showed that HAS could upregulate the expressions of p-PI3k, Akt, p-Akt, and Bcl-2, while it could downregulate the expressions of cleaved caspase-3 and Bax in H2O2-stimulated PC12 cells. Collectively, it could be concluded according to our results that HAS possesses protective potentials on H2O2-stimulated PC12 cells through suppression of oxidative stress-induced apoptosis via regulation of PI3K/Akt signal pathway.