Supplementation of Crataegi fructus alleviates functional dyspepsia and restores gut microbiota in mice.

Introduction: Functional dyspepsia (FD), also known as non-ulcerative dyspepsia, is a common digestive system disorder. Methods: In this study, an FD model was established using hunger and satiety disorders combined with an intraperitoneal injection of L-arginine. Indices used to evaluate the efficacy of hawthorn in FD mice include small intestinal propulsion rate, gastric residual rate, general condition, food intake, amount of drinking water, gastric histopathological examination, and serum nitric oxide (NO) and gastrin levels. Based on the intestinal flora and their metabolites, short-chain fatty acids (SCFAs), the mechanism of action of Crataegi Fructus (hawthorn) on FD was studied. The fecal microbiota transplantation test was used to verify whether hawthorn altered the structure of the intestinal flora. Results: The results showed that hawthorn improved FD by significantly reducing the gastric residual rate, increasing the intestinal propulsion rate, the intake of food and drinking water, and the levels of gastrointestinal hormones. Simultaneously, hawthorn elevated substance P and 5-hydroxytryptamine expression in the duodenum, reduced serum NO levels, and increased vasoactive intestinal peptide expression in the duodenum. Notably, hawthorn increased the abundance of beneficial bacteria and SCFA-producing bacteria in the intestines of FD mice, decreased the abundance of conditional pathogenic bacteria, and significantly increased the SCFA content in feces. Discussion: The mechanism by which hawthorn improves FD may be related to the regulation of intestinal flora structure and the production of SCFAs.

Jasminoidin and ursodeoxycholic acid exert synergistic effect against cerebral ischemia-reperfusion injury via Dectin-1-induced NF-κB activation pathway.

BACKGROUND: Jasminoidin (JA) and ursodeoxycholic acid (UA) were shown to act synergistically against ischemic stroke (IS) in our previous studies. PURPOSE: To investigate the holistic synergistic mechanism of JA and UA on cerebral ischemia. METHODS: Middle cerebral artery obstruction reperfusion (MCAO/R) mice were used to evaluate the efficacy of JA, UA, and JA combined with UA (JU) using neurological function testing and infarct volume examination. High-throughput RNA-seq combined with computational prediction and function-integrated analysis was conducted to gain insight into the comprehensive mechanism of synergy. The core mechanism was validated using western blotting. RESULTS: JA and UA synergistically reduced cerebral infarct volume and alleviated neurological deficits and pathological changes in MCAO/R mice. A total of 1437, 396, 1080, and 987 differentially expressed genes were identified in the vehicle, JA, UA, and JU groups, respectively. A strong synergistic effect between JA and UA was predicted using chemical similarity analysis, target profile comparison, and semantic similarity analysis. As the 'long-tail' drugs, the top 20 gene ontology (GO) biological processes of JA, UA, and JU groups primarily reflected inflammatory response and regulation of cytokine production, with specific GO terms of JU revealing enhanced regulation on immune response and tumor necrosis factor superfamily cytokine production. Comparably, the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling of common targets of JA, UA, and JU focused on extracellular matrix organization and signaling by interleukins, immune system, phagosomes, and lysosomes, which interlock and interweave to produce the synergistic effects of JU. The characteristic signaling pathway identified for JU highlighted the crosstalk between autophagy activation and inflammatory pathways, especially the Dectin-1-induced NF-κB activation pathway, which was validated by in vivo experiments. CONCLUSIONS: JA and UA can synergistically protect cerebral ischemia-reperfusion injury by attenuating Dectin-1-induced NF-κB activation. The strategy integrating high throughput data with computational models enables ever-finer mapping of 'long-tail' drugs to dynamic variations in condition-specific omics to clarify synergistic mechanisms.

The role of traditional herbal medicine for ischemic stroke: from bench to clinic-A critical review.

BACKGROUND: Ischemic stroke (IS) is a leading cause of death and severe long-term disability worldwide. Over the past few decades, considerable progress has been made in anti-ischemic therapies. However, IS remains a tremendous challenge, with favourable clinical outcomes being generally difficult to achieve from candidate drugs in preclinical phase testing. Traditional herbal medicine (THM) has been used to treat stroke for over 2,000 years in China. In modern times, THM as an alternative and complementary therapy have been prescribed in other Asian countries and have gained increasing attention for their therapeutic effects. These millennia of clinical experience allow THM to be a promising avenue for improving clinical efficacy and accelerating drug discovery. PURPOSE: To summarise the clinical evidence and potential mechanisms of THMs in IS. METHODS: A comprehensive literature search was conducted in seven electronic databases, including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure, the VIP Information Database, the Chinese Biomedical Literature Database, and the Wanfang Database, from inception to 17 June 2022 to examine the efficacy and safety of THM for IS, and to investigate experimental studies regarding potential mechanisms. RESULTS: THM is widely prescribed for IS alone or as adjuvant therapy. In clinical trials, THM is generally administered within 72 h of stroke onset and are continuously prescribed for over 3 months. Compared with Western medicine (WM), THM combined with routine WM can significantly improve neurological function defect scores, promote clinical total effective rate, and accelerate the recovery time of stroke with fewer adverse effects (AEs). These effects can be attributed to multiple mechanisms, mainly anti-inflammation, antioxidative stress, anti-apoptosis, brain blood barrier (BBB) modulation, inhibition of platelet activation and thrombus formation, and promotion of neurogenesis and angiogenesis. CONCLUSIONS: THM may be a promising candidate for IS management to guide clinical applications and as a reference for drug development.

Precise Investigation of the Efficacy of Multicomponent Drugs Against Pneumonia Infected With Influenza Virus.

Background: Viral pneumonia is one of the most serious respiratory diseases, and multicomponent traditional Chinese medicines have been applied in the management of infected patients. As a representative TCM, HouYanQing (HYQ) oral liquid shows antiviral activity. However, the unclear mechanisms, as well as the ambiguous clinical effects, limit widespread application of this treatment. Therefore, in this study, a proteomics-based approach was utilized to precisely investigate its efficacy. Methods: Based on the efficacy evaluation of HYQ in a mouse model of pneumonia caused by influenza A virus (H1N1) and the subsequent proteomics analysis, specific signatures regulated by HYQ treatment of viral pneumonia were identified. Results: Experimental verifications indicate that HYQ may show distinctive effects in viral pneumonia patients, such as elevated galectin-3-binding protein and glutathione peroxidase 3 levels. Conclusion: This study provides a precise investigation of the efficacy of a multicomponent drug against viral pneumonia and offers a promising alternative for personalized management of viral pneumonia.

Network pharmacology integrated with molecular docking reveals the common experiment-validated antipyretic mechanism of bitter-cold herbs.

ETHNOPHARMACOLOGICAL RELEVANCE: Bitter-cold herbs have been used to clearing heat and expelling damp in clinical practice in China for thousands of years. AIM OF THE STUDY: This study aimed to investigate the common molecular mechanism of bitter-cold herbs through network pharmacology analysis, molecular docking and experimental validation in vivo. MATERIALS AND METHODS: Network pharmacological analysis integrated with molecular docking was employed to identify the active compounds and core action targets of the bitter-cold herbs. Then, the yeast-induced pathological model was established, and the antipyretic effect of the herbs was evaluated by checking rectal temperatures of the mice hourly. Lastly, the protein expression of core targets was examined to reveal the antipyretic mechanism. RESULTS: A total of 52 lead compounds from the four bitter-cold herbs, Phellodendri Chinensis Cortex (PCC), Sophorae Flavescentis Radix (SFR), Gentianae Radix Et Rhozima (GRER) and Coptidis Rhizoma (CR), and 248 compounds-related targets were screened out with PTGS2 ranking the first. The results from molecular docking showed that 22 compounds adopted the same orientation as aspirin and had an excellent stability in the active site pocket of PTGS2. Furthermore, these herbs exerted potential therapeutic effects through 38 related pathways. On the other hand, the outcome of animal experiments showed that they could significantly attenuate the yeast-induced mice fever with dose-dependent relationship. Further experimental results demonstrated that administration of yeast suspension raised protein expression of PTGS2 significantly, which was evidently inhibited in the high or low-dose groups of GRER as well as in the low-dose group of SFR (P < 0.01) though a higher expression of PTGS2 was shown in the low-dose group of CR compared with FM group (P < 0.01). CONCLUSIONS: The bitter-cold herbs can alleviate fever response and their antipyretic effect may mainly be attributed to regulating the expression of PTGS2 after the formation of ligand-receptor/PTGS2 complexes, and their active compounds might be nominated as antipyretic lead-ligand candidates.

Efficacy of Yiqigubiao pill on chronic obstructive pulmonary disease in rats with the disease induced by lipopolysaccharide and cigarette-smoke fumigation.

OBJECTIVE: To investigate the efficacy of Yiqigubiao pill (YQGB) on chronic obstructive pulmonary disease (COPD) in rats with the COPD induced by lipopolysaccharide (LPS) and cigarette- smoke fumigation. METHODS: In this study, six groups of rats were set up, including control group, model group, positive control group (aminophylline) and YQGB (high, medium and low doses) groups. Tracheal injection of lipopolysaccharide (LPS) and cigarette-smoke fumigation induced COPD in rats. The general condition, incubation period and coughing times, lung function, level of inflammatory factors, leukocyte condition and pathological changes of bronchus and lung tissue were observed in rats of each group. RESULTS: In the COPD rats, the latent period of coughing was shortened and the cough frequency was increased significantly; the pulmonary function was significantly decreased, which was manifested by the increased lung tissue resistance and respiratory system resistance, and the decreasing percentage of forced expiratory volume and forced expiratory volume in the 0.3 s (FEV0.3/FVC); the contents of tumor necrosis factor-alpha (TNF-α) and interleukin-4 in serum were obviously increased, and the NEUT% in bronchoalveolar lavage fluid was significantly increase. YQGB could obviously prolong the latent period of cough, and reduce the cough frequency and the content of TNF-α in serum. YQGB can also significantly reduce respiratory resistance and increase FEV0.3/FVC value. The results of histopathology showed that YQGB significantly reduced the pathological changes of tracheal mucosa and lung caused by COPD. YQGB obviously increased level of AQP1, which was down-regulated in the COPD rats. CONCLUSION: YQGB could significantly improve the pulmonary function, reduce inflammation and alleviate lung and bronchial diseases in the COPD rats.

Intermodule Coupling Analysis of Huang-Lian-Jie-Du Decoction on Stroke.

Huang-Lian-Jie-Du Decoction (HLJDD) is a "Fangji" made up of well-designed Chinese herb array and widely used to treat ischemic stroke. Here we aimed to investigate pharmacological mechanism by introducing an inter-module analysis to identify an overarching view of target profile and action mode of HLJDD. Stroke-related genes were obtained from OMIM (Online Mendelian Inheritance in Man). And the potential target proteins of HLJDD were identified according to TCMsp (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform). The two sets of molecules related to stroke and HLJDD were respectively imported into STRING database to construct the stroke network and HLJDD network, which were dissected into modules through MCODE, respectively. We analyzed the inter-module connectivity by quantify "coupling score" (CS) between HLJDD-modules (H-modules) and stroke-modules (S-module) to explore the pharmacological acting pattern of HLJDD on stroke. A total of 267 stroke-related proteins and 15 S-modules, 335 HLJDD putative targeting proteins, and 13 H-modules were identified, respectively. HLJDD directly targeted 28 proteins in stroke network, majority (16, 57.14%) of which were in S-modules 1 and 4. According to the modular map based on inter-module CS analysis, H-modules 1, 2, and 8 densely connected with S-modules 1, 3, and 4 to constitute a module-to-module bridgeness, and the enriched pathways of this bridgeness with top significance were TNF signaling pathway, HIF signaling pathway, and PI3K-Akt signaling pathway. Furthermore, through this bridgeness, H-modules 2 and 4 cooperatively work together to regulate mitochondrial apoptosis against the ischemia injury. Finally, the core protein in H-module 4 account for mitochondrial apoptosis was validated by an in vivo experiment. This study has developed an integrative approach by inter-modular analysis for elucidating the "shotgun-like" pharmacological mechanism of HLJDD for stroke.

[Effect of fresh Gastrodia elata on gut microbiota in mice].

Gastrodia elata B1.,a traditional Chinese medicine,was frequently applied as a cure for headache or migraine. Its effects include suppressing hyperactive liver,calming endogenous wind,dredging collateralsand relieving spasm. There has been a proportion that G. elata should be added to The List of Substances That Are Traditionally Both Food and Chinese Medicinal Materials. The dry G. elata was commonly used in clinic,which have some fundamental study on efficacy and mechanism. However,fresh G. elata,which was added to herbal cuisine very often,lacks corresponding research. The interaction of diet,microbiota and human is a hot issue and lots of scholars are focusing on it. This research sequenced the 16 S rRNA of mouse cecal contents on Mi Seq platform to understand the effect of taking fresh G. elata. As the results showing,multiple probiotics grew after taking fresh G. elata extract,including Ruminiclostridium,Butyricicoccus,and Parvibacter. To contrast,some pathogens or potential pathogens,such as Escherichia/Shigella,Parasutterella,decreased. This manifests that fresh G. elata performs a positive regulation on mouse gut microbiota,especially the low-dose fresh G. elata extraction could restructure the microbiota apparently. Our result reveals that microbiota might be a new target for G. elata extract and provides an important basis for further research on the interaction between gut microbiota and pharmacological activity of G. elata.

[Analysis of protective effects of Chaihu Jia Longgu Muli Tang against ischemic stroke by combining traditional Chinese medicine pathogenesis and efficacy with modern pathology and pharmacology].

Chaihu Jia Longgu Muli Tang is a classical Chinese formulas treating Shaoyang syndrome complicated with Yangming syndrome according to Treatise on Febrile Diseases. This formula is used in mental disorder, nervous system, gynecologic, andrologic, and cardiovascular disease. However, its therapeutic effect on ischemia stroke and its mechanism is far from clear. In clinical practice, we have found that this formula is effective in treating ischemic stroke, which can shorten the course of the disease and reduce recurrence. The characteristics of this formula include: Shaoyang cardinal disadvantageous syndrome, mental and nervous symptoms, retained fluid punched upward syndrome and accumulation of heat in the stomach and intestines. By combining traditional Chinese medicine (TCM) pathogenesis and efficacy with modern pathology and pharmacology, we proposed that the TCM pathogenesis of stroke, which is characterized by hyperactivity of heat combining with phlegm, stasis and water drink, is consistent with syndromes and corresponding pathology targeted by Chaihu Jia Longgu Muli Tang, including the stress brain edema zone around the ischemic lesion, the increase of intracranial pressure, the excitement of sympathetic nerve, the release of monoamine neurotransmitter, the hypofunction of autonomic nervous system after stroke, and gastrointestinal stress response. Furthermore, the pharmacological mechanism of Chaihu Jia Longgu Muli Tang is concentrated on regulation the neuroendocrinology system centered by hypothalamic-pituitary-adrenal axis (HPA), participating in the process of neuron regeneration and apoptosis, oxidative stress, hyperactivity of sympathetic nerve, and inflammatory reaction. These pathological processes are consistent with the pathological changes after ischemic stroke. Therefore, Chaihu Jia Longgu Muli Tang is a key formula for treating ischemic stroke.

[Pharmacodynamic evaluation and molecular mechanism research of Huanshao capsule on irregular menstruation].

Huanshao capsule is widely used in irregular menstruation and has achieved a good effect. Huanshao capsule can promote gonad development in mice, significantly improve the ovarian index in mice, increase estrogen level and reduce FSH level in rats, inhibit the pain response induced by oxytocin and estrogen, inhibit writhing reaction induced by acetic acid pain in mice. Due to the complexity of traditional Chinese medical formula, the pharmacological mechanism of the treatment on the irregular menstruation of the Huanshao capsule is unclear. In this study, the internet-based computation platform (www.tcmip.cn）was used to explore the molecular mechanism of Huanshao capsule on the menstrual. The aim of this study was to find the molecular mechanism of Huanshao capsule in treating menstrual. In the study of the molecular mechanism of Huanshao capsule in the treatment of menstrual by using the internet-based computation platform, Huanshao capsule maybe treat the menstrual by the pathway of endocrine system, GnRH signal transduction pathway, estrogen signal transduction pathway, oxytocin signaling pathway, thyroid hormone signaling pathway, VEGF signaling pathway, FCεRI signaling pathway and purine metabolism and nucleotide metabolism. The early pharmacological study confirmed Huanshao capsule could increase the serum estradiol level and decrease follicle stimulating hormone level and the traditional Chinese medicine pharmacology coincide with the prediction result of internet-based computation platform which roles as the pathway of GnRH signaling pathway and estrogen signal transduction pathway. Other pathway needs further experimental verification.

[Comparative pharmacodynamics study on Paris forrestii and pharmacopoeial Paridis Rhizoma].

Paris is a raw material of a variety of Chinese medicines, which has become deficient in resource due to market demand substantial growth and wild Paris resources reducing increasingly and the artificial cultivation slow growth. This study compared pharmacological activity in analgesia and anti-inflammatory and hemostasis effects of P. forrestii with pharmacopoeial Paridis Rhizoma to expand its range of Paris medicinal resources and protect wild resources of Paris and meet market demand. The experimental study showed that P. forrestii and P. polyphylla var. yunnanensis and P. polyphylla var. chinensis had analgesic, anti-inflammatory and hemostatic effects. They can significantly reduce the number of writhing and inhibit rat foot swelling induced by carrageenan and mice capillary permeability induced by acetic acid and short the bleeding time and clotting time. Their function is equivalent.

[Pharmacodynamics study on Paris vietnamensis].

Paris is commonly used in traditional Chinese medicine and its resource is in shortage, a variety of related plants are acquired as Paris. This study compared pharmacological activity in anti-inflammatory and hemostatic and blood rheology of P. vietnamensis with pharmacopoeial Paridis Rhizoma to expand its range of Paris medicinal resources and protect wild resources of Paris and meet market demand. The experimental study showed that P. vietnamensis and P. polyphylla var. yunnanensis and P. polyphylla var. chinensis had anti-inflammatory and hemostatic effect and improved blood rheolog. They can significantly inhibit rat foot swelling induced by carrageenan and short the bleeding time and clotting time and reduce the blood viscosity in rats with acute blood stasis model, P. vietnamensis and P. polyphylla var. yunnanensis can inhibit mice capillary permeability induced by acetic acid.

A Chinese Herbal Decoction, Shaoyao-Gancao Tang, Exerts Analgesic Effect by Down-Regulating the TRPV1 Channel in a Rat Model of Arthritic Pain.

Shaoyao-Gancao Tang (SGT) is one of the most frequently used compound formulas in the treatment of pain-related diseases in the medical practice of traditional Chinese medicine (TCM). To investigate the anti-inflammatory and antinociceptive effects, as well as to uncover the molecular mechanism of SGT, the rat pain model of arthritis was experimentally induced by single unilateral injection of rats' left hind paw with Freund's complete adjuvant (FCA). SGT was orally administered to the rats daily at three doses individually for a period of 16 days post-model induction. Swollen degrees and pain thresholds of the rats in different groups were measured for evaluation of the anti-inflammatory and anti-nociceptive effects of SGT. Furthermore, the mRNA and protein expression levels of transient receptor potential ion channel protein vanilloid receptor 1 (TRPV1) channel as well as its calcium-mediating function in the isolated DRG neurons were further detected to provide indexes for exploration of the molecular mechanisms mediating anti-arthritic activities of SGT. As a result, FCA injection induced significant allodynia, inflammation and edema, accompanied by a significant increase in both expression and calcium-mediating function of the TRPV1 channel. Pharmacologically, oral administration of SGT at a high or middle dose demonstrated a significant relief from the above-mentioned pathological conditions in a dose-dependent manner. Simultaneously the mRNA and protein expressional levels of TRPV1 channel, as well as its calcium-mediating function, were down-regulated greatly. These findings suggest that SGT possesses a significant analgesic and anti-inflammatory effect on arthritis rats; its therapeutic activities might be achieved through reversing the elevated expression and function of TRPV1 channel evoked by FCA.

Differential mechanistic investigation of protective effects from imperatorin and sec-O-glucosylhamaudol against arsenic trioxide-induced cytotoxicity in vitro.

BACKGROUND AND PURPOSE: The clinical use of arsenic trioxide (As2O3) for treating acute promyelocytic leukemia (APL) is limited due to its severe cardiotoxicity. The possible mechanisms of As2O3-induced cardiotoxicity include DNA fragmentation, reactive oxygen species (ROS) generation, cardiac ion channel changes and apoptosis. The present study is designed to investigate the protective effects of imperatorin and sec-O-glucosylhamaudol and to explore their mechanistic involvement in As2O3-induced cytotoxicity. EXPERIMENTAL METHODS: Cell viability assay, Lactate dehydrogenase (LDH) release, Acridine orange/ethidium bromide (AO/EB) double staining, Caspase-3 activity assay, ROS generation, cellular calcium levels, mRNA expression levels by qRT-PCR and protein expression levels by Western blotting were measured in H9c2 cells in combination with As2O3 and imperatorin or sec-O-glucosylhamaudol. KEY RESULTS: We observed that H9c2 cells treated with imperatorin or sec-O-glucosylhamaudol were more resistant to As2O3-induced cell death. Both imperatorin and sec-O-glucosylhamaudol reduced H9c2 cell apoptosis, but both imperatorin and sec-O-glucosylhamaudol had no effects on Caspase-3 activity and intracellular calcium accumulation. Furthermore, imperatorin was capable of suppressing ROS generation, while sec-O-glucosylhamaudol did not show this effect. Moreover, imperatorin and sec-O-glucosylhamaudol triggered Nrf2 activation, which resulted in upregulation of downstream phase II metabolic enzymes and antioxidant protein/enzyme, probably offering cellular protection to As2O3-induced cardiotoxicity via the Nrf2 signal pathway. CONCLUSIONS AND IMPLICATIONS: Imperatorin and sec-O-glucosylhamaudol can ameliorate As2O3-induced cytotoxicity and apoptosis in H9c2 cells, the mechanisms probably related to antioxidation. As2O3 in combination with imperatorin or sec-O-glucosylhamaudol could be considered as a novel strategy to expand the clinical application of As2O3.

The rhizome of Gastrodia elata Blume - An ethnopharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodia elata Blume (Orchidaceae) is commonly called Tian ma in Chinese and mainly distributed in the mountainous areas of eastern Asia, such as China, Korea, Japan and India. It is an extensively used traditional Chinese herbal medicine in the clinical practice of traditional Chinese medicine, to treat headache, migraine, dizziness, epilepsy, infantile convulsion, tetany and so on. The present paper reviews the advancements in investigation of botany and ethnopharmacology, phytochemistry, pharmacology, toxicology and quality control of Gastrodia elata Blume. Finally, the possible tendency and perspective for future investigation of this plant are also put forward. MATERIALS AND METHODS: The information on Gastrodia elata Blume was collected via piles of resources including classic books about Chinese herbal medicine, and scientific databases including Pubmed, Google Scholar, ACS, Web of science, ScienceDirect databases, CNKI and others. Plant taxonomy was validated by the databases "The Plant List", and "Mansfeld's Encyclopedia". RESULTS: Over 81 compounds from this plant have been isolated and identified, phenolics and polysaccharides are generally considered as the characteristic and active constituents of Gastrodia elata Blume. Its active compounds possess wide-reaching biological activities, including sedative, hypnotic, antiepileptic, anticonvulsive, antianxietic, antidepressant, neuroprotective, antipsychotic, anti-vertigo, circulatory system modulating, anti-inflammationary, analgesic, antioxidative, memory-improving and antiaging, antivirus and antitumor effects. CONCLUSION: Despite the publication of various papers on Gastrodia elata Blume, there is still, however, the need for definitive research and clarification of other bioactive compounds using bioactivity-guided isolation strategies, and the possible mechanism of action as well as potential synergistic or antagonistic effects of multi-component mixtures derived from Gastrodia elata Blume need to be evaluated. It is also necessary and important to do more quality control and toxicological study on human subjects in order to maintain its efficacy stable in the body and validate its safety in clinical uses. In addition, more investigations on other parts of this plant beyond the tubers are needed. Further studies on Gastrodia elata Blume will lead to the development of new drugs and therapeutics for various diseases, and how to utilize it better should be paid more attention to.

Antitumor activities of biscoumarin and dihydropyran derivatives.

Rising worldwide cancer incidence and resistance to current anti-cancer drugs necessitate the need for new pharmaceutical compounds and drug delivery system. Two novel series of biscoumarin (1-4) and dihydropyran (5-16) derivatives were synthesized via a one-pot multicomponent condensation reaction and evaluated for their antitumor activity in vitro. The X-ray crystal structure analysis of four representative compounds 2, 7, 10 and 13 confirmed the structures of these compounds. Compounds 1-4 showed the most potent antitumor activity among the total 16 derivatives. More interestingly, preliminary mechanism studies revealed that the most potent compound 4 induced apoptosis and arrested the cell cycle at the S phase in HUTU80 cells. Additionally, the increased accumulation of HUTU80 cells in the sub G1 peak further pointed to the occurence of the cell apoptosis. The selectivity index analysis demonstrated that all the biscoumarin compounds (SI=3.1-7.5) possess higher selectivity towards intestinal epithelial adenocarcinoma cell line (HuTu80) than positive control drug carboplatin (SI=1.6-1.8). The biscoumarin compounds also showed no obvious acute toxicity on mice.

[TRPV1 channel-mediated thermogenesis is a common mode for the Chinese pungent-hot or pungent-warm herbs to demonstrate their natures].

To further uncover the scientific significance and molecular mechanism of the Chinese herbs with pungent hot or warm natures, endogenous and exogenous expression systems were established by isolation of dorsal root ganglion (DRG) neurons and transfection of HEK293 cells with TRPV1 channel gene separately. On this basis, the regulation action of capsaicin, one main ingredient from chili pepper, on TRPV1 channel was further explored by using confocal microscope. Besides, the three-sites one-unit technique and method were constructed based on the brown adipose tissue (BAT), anal and tail skin temperatures. Then the effect of capsaicin on mouse energy metabolism was evaluated. Both endogenous and exogenous TRPV1 channel could be activated and this action could be specifically blocked by the TRPV1 channel inhibitor capsazepine. Simultaneously, the mice's core body temperature and BAT temperature fall down and then go up, accompanied by the increase of temperature of the mice's tail skin. Promotion of the energy metabolism by activation of TRPV1 channel might be the common way for the pungent-hot (warm) herbs to demonstrate their natures.

Synthesis of biscoumarin and dihydropyran derivatives with promising antitumor and antibacterial activities.

Two series of biscoumarin (1-3) and dihydropyran (4-12) derivatives were successfully synthesized as new antitumor and antibacterial agents. The molecular structures of four representative compounds 2, 4, 7 and 10 were confirmed by single crystal X-ray diffraction study. The synthesized compounds (1-12) were evaluated for their antitumor activities against human intestinal epithelial adenocarcinoma cell line (HuTu80), mammary adenocarcinoma cell line (4T1) and pancreatic cancer cell line (PANC1) and antibacterial activities against one drug-sensitive Staphylococcus aureus (S. aureus ATCC 29213) strain and three MRSA strains (MRSA XJ 75302, Mu50, USA 300 LAC). The further mechanism study demonstrated that the most potent compound 1 could obviously inhibit the proliferation of cancer cells via the mechanism to induce apoptosis.

Antibacterial and Antitumor Activities of Biscoumarin and Dihydropyran Derivatives.

A novel series of biscoumarin (1-4) and dihydropyran (5-13) derivatives were synthesized via a one-pot multicomponent condensation reaction and evaluated for antibacterial and antitumor activity in vitro. The X-ray crystal structure analysis of four representative compounds, 3, 7, 9 and 11, confirmed the structures of these compounds. Compounds 1-4 showed the most potent antitumor activity among the total 13 derivatives; especially for compounds 1 and 2, they also emerged as promising antibacterial members with better antibacterial activity. In addition, the results of density functional theory (DFT) showed that compared with compounds 3 and 4, biscoumarins 1 and 2 had lower intramolecular hydrogen bonds (HB) energy in their structures.

Chemistry and pharmacology of Siraitia grosvenorii: a review.

Siraitia grosvenorii is a perennial herb endemic to Guangxi province of China. Its fruit, commonly known as Luo hanguo, and has been used for hundreds of years as a natural sweetener and as a traditional medicine for the treatment of pharyngitis, pharyngeal pain, as well as an anti-tussive remedy in China. Based on ninety-three literary sources, this review summarized the advances in chemistry, biological effects, and toxicity research of S. grosvenorii during the past 30 years. Several different classes of compounds have been isolated or detected from various parts of S. grosvenorii, mainly triterpenoids, flavonoids, polysaccharides, amino acids, and essential oils. Various types of extracts or individual compounds derived from this species exhibited a wide array of biological effects e.g. anti-tussive, phlegm-relieving, anti-oxidant, immunomodulatory, liver-protecting, glucose-lowering, and anti-microbial. The existing research has shown that extracts and individual compounds from S. grosvenorii are basically non-toxic. Finally, some suggestions for further research on specific chemical and pharmacological properties of S. grosvenorii are proposed in this review.