Traditional System Of Medicine Research Articles

A Therapeutic Evaluation of Anticancer and Pharmacological Abilities on Tinospora cordifolia: A Systematic Review

Tinospora cordifolia (Tc), commonly called as Giloy, it is a herbaceous vine that is widely used in traditional medicine systems for its alleged anti-cancer effects. The purpose of this systematic study is to assess Tinospora cordifolia’s (Tc) medicinal potential against cancer. A thorough search of various scientific databases was done for studies looking at Tinospora cordifolia's anti-cancer properties. The findings demonstrate a varied variety of In vitro and In vivo research demonstrating Tinospora cordifolia’s (Tc) anti-proliferative, apoptotic and anti-metastatic activities against many cancer types, including breast, prostate, colon, and leukaemia. Mechanistic insights into its mode of action, such as modulation of signaling pathways involved in cell cycle regulation, apoptosis and angiogenesis, are presented. However, limitations in study designs, inconsistency in methodology, and differences in reported outcomes highlight the need for more well-designed clinical trials to evaluate Tinospora cordifolia's efficacy and safety as a potential supplementary medicine in cancer treatment regimens. Therapeutic plants, such as T. cordifolia, can strengthen the body's defences against disease and cure specific areas, displaying more body compatibility and fewer side effects than medications. In conjunction with this, the current study highlights T. cordifolia's pharmacological potential against a variety of illnesses.

Occurrence, Isolation, Pharmacological Potential, Metabolism, and Toxicity of Myristicin: A Naturally Occurring Alkoxy-Substituted Allylbenzene

Background: Natural products are secondary metabolites obtained from plants, animals, and microorganisms with diverse chemical structures resulting in diverse biological functions and drug-like properties. Objective: This review article summarizes in detail the occurrence, detection, isolation, various pharmacological properties, metabolism, and toxicity of a natural compound i.e., 5-Allyl-1-methoxy- 2,3-methylenedioxybenzene commonly known as Myristicin. Methods: A relevant literature search was made using the keywords essential oil, mace, myristicin, nutmeg, and pharmacological activities from different databases such as PubMed, Sci Finder, Science Direct, and Google Scholar. The literature search results presented articles from 1963 to 2022. Thereafter, the articles were carefully screened and selected for review. Results: Myristicin, an alkoxy-substituted allylbenzene is present in major to minor amounts in the essential oils obtained from different plant parts and exhibits various pharmacological properties such as antimicrobial, antioxidant, antiproliferative, anti-inflammatory, insecticidal, and hepatoprotective. It forms 10 metabolites by reduction, demethylation, hydroxylation, ring formation, ring-opening, and conjugate formation. In the liver, myristicin has been metabolized by Cytochrome P450 complex enzymes to generate active metabolite (1ˈ hyroxymyristicin) responsible for cytotoxic, genotoxic and apoptotic effects (150 μM). But, myristicin at 600 μM does not produce enough 1ʼ-hydroxymyristicin to give the final toxicant. Conclusion: Myristicin poses no major risk to human health through the consumption of herbs and spices due to its presence in low amounts. It has great potential to be used in the traditional system of medicine. We hope that this review will provide complete knowledge about myristicin on a single platform.

Exploring the potential of the traditional Indian system of medicine, Ayurveda, for developing an evidence-based integrative model of cancer care in elderly patients with cancer.

e13527 Background: Available evidence suggests that age is a deterrent to accepting cancer-directed treatment, with up to 38% of advanced-stage elderly cancer patients declining conventional anticancer therapy. Such patients opt for various complementary and alternative medicine (CAM). Considering the paucity of available evidence about CAM, it is necessary that the outcomes of CAM in elderly cancer patients should be studied and an evidence-based integrated model for cancer care should be developed. In the present study, we evaluated various characteristics and outcomes of elderly cancer patients from India who voluntarily opt for Ayurveda cancer therapy, either after having a persistent disease after completing conventional therapies or declining conventional therapy. Methods: This observational study was conducted on the elderly population (age> 65 years) approaching treatment at our specialty Ayurveda cancer clinic in India. Data about demography, comorbidity, and efficacy outcome variables like QoL (FACT-G), Performance status (ECOG), anxiety and depression (HADS) was obtained through chart review based on the computerized database of patients who approached treatment between years 2020 to 2023. This being a preliminary proof of concept study the obtained data was subjected to per protocol analysis for avoiding the effect of various confounding variables which can lead to dropouts and poor compliance. As such, study analysis includes only those patients who completed at least 180 days of treatment with more than 80% compliance to the therapy for at least 6 months. Results: From database of 1010 elderly cancer patients, data from 172 patients (92 males and 80 females) who fulfilled the eligibility criteria was selected. Amongst the total sample size, 131 patients were of stage III and IV. The number of patients with uncontrolled hypertension, uncontrolled diabetes, and a history of cardiovascular accidents was 45 (26.1%), 83 (48.2%) and 8 (4.6%) respectively. More than one comorbidity was present in 70 patients (40.6%), whereas 64 patients (37%) patients voluntarily refused anticancer therapies. The duration of treatment was 459.58 (±246.89) days. At the end of 90 and 180 days, a significant improvement was observed in Qol, Performance status, depression, and anxiety (all P>0.01). Conclusions: This study suggests that amongst the elderly Indian cancer patients who opt for Ayurveda therapy, around 38% of them decline conventional therapy whereas others opt for Ayurveda therapy after completing conventional anti-cancer therapies. Ayurveda therapy has been shown to improve health-related Quality of life, performance status, anxiety, and depression. This finding warrants further prospective pragmatic studies which can act as a basis to develop an evidence-based integrative model for cancer care in the elderly population.

Network pharmacology prediction and experiment validation of anti-liver cancer activity of Curcumae Rhizoma and Hedyotis diffusa Willd

Objective: This study aims to elucidate anti-liver cancer components and potential mechanisms of Curcumae Rhizoma and Hedyotis diffusa Willd (CR-HDW). Methods: Effective components and targets of CR-HDW were identified from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Liver cancer-related genes were collected from GeneCards, Gene-Disease Association (DisGeNET), and National Center for Biotechnology Information (NCBI). Protein-protein interaction networks, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were conducted to analyze the identified genes. Molecular docking was used to simulate binding of the active components and their target proteins. Cell activity assay, western blot, and senescence-associated β-galactosidase (SA-β-gal) experiments were conducted to validate core targets identified from molecular docking. Results: Ten active compounds of CR-HDW were identified including quercetin, 3-epioleanic acid and hederagenin. The primary core proteins comprised Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Protein Kinase B(AKT1), etc. The pathways for Phosphoinositide 3-kinase (PI3K)/ AKT, cellular senescence, Fork head boxO (FOXO) were revealed as important for anti-cancer activity of CR-HDW. Molecular docking demonstrated strong binding between liver cancer target proteins and major active components of CR-HDW. In-vitro experiments confirmed that hederagenin and 3-epioleolic acid inhibited HuH-7 cell growth, reduced expression of PI3K, AKT, and mechanistic target of rapamycin (mTOR) proteins. Hederagenin also induced HuH-7 senescence. Conclusions: In summary, The authors’ results suggest that the CR-HDW component (Hederagenin, 3-epoxy-olanolic acid) can inhibit the proliferation of HuH-7 cells by decreasing PI3K, AKT, and mTOR. Hederagenin also induced HuH-7 senescence.

Exploring the multicomponent synergy mechanism of Zuogui Wan on postmenopausal osteoporosis by a systems pharmacology strategy.

To explore the multi-component synergistic mechanism of Zuogui Wan (, ZGW) in treating postmenopausal osteoporosis (PMOP). The main components and target genes of ZGW were screened via the Traditional Chinese Medicine Systems Pharmacology (TCMSP). In addition, the target gene sets of PMOP were derived from the GeneCards and Online Mendelian Inheritance in Man databases. The search tool for recurring instances of neighbouring genes (STRING) 11.0 software was used to analyze the interaction among intersecting genes. Cytoscape 3.6.1 software and the Matthews correlation coefficient (MCC) algorithm were used to screen the core genes. Fifty Sprague-Dawley female rats were randomly divided into the sham-operated (Sham) group and the four ovariectomized (OVX) subgroups. Rats subjected to Sham or OVX were administered with the vehicle (OVX, 1 mL water/100 g weight), 17β-estradiol (E2, 50 μg·kg-1·d-1), and lyophilized powder of ZGW at a low dose of 2.3 (ZGW-L) and high dose of 4.6 (ZGW-H) g·kg-1·d-1 for three months. The bone density and bone strength were assessed using dual-energy X-ray and three-point bending tests, respectively. Furthermore, enzyme-linked immun-osorbent assay, Hematoxylin-eosin staining, and western blot analysis were used to determine the potential pharmacological mechanisms of action of ZGW in PMOP. A total of 117 active compounds of ZGW were screened from the TCMSP. Furthermore, 108 intersecting genes of drugs and diseases were identified. Using STRING software and the MCC algorithm, ten core genes, including C-X-C chemokine living 8 (CXCL8), C-C chemokine receptor type 2 (CCR2), alpha-2a active receptor (ADRA2A), melatonin receptor type 1B (MTNR1B), and amyloid-beta A4 protein (APP), were identified. The anti-osteoporosis regulation network of ZGW was constructed using the Cytoscape software. The animal experiments demonstrated that ZGW groups significantly reduced the serum levels of β-C-terminal telopeptide of type I collagen (β-CTX) and increased serum levels of bone-specific alkaline phosphatase (BALP) (P < 0.05, P < 0.01). The OVX group exhibited a significant decrease in bone mineral density and bone strength compared with the Sham group (P < 0.01). Moreover, treatment with ZGW resulted in increased trabecular thickness, improved arrangement of trabecular structure, and reduced empty bone lacunae. Furthermore, treatment with ZGW significantly increased the protein expression of CXCL8, ADRA2A, and CCR2 (P < 0.05, P < 0.01), and significantly decreased the protein expression of Runx2 (P < 0.01). Furthermore, the ZGW and E2 groups demonstrated significantly increased BMD (P < 0.05, P < 0.01), improved bone strength (P < 0.05, P < 0.01), reduced expression of CXCL8, ADRA2A, and CCR2, and increased runt-related transcription factor 2 levels in bone tissue (P < 0.05, P < 0.01) compared with the OVX group. However, there were no significant differences in MTNR1B and APP expression among the groups. ZGW shows synergistic mechanisms in PMOP through multiple components, targets, and pathways.

Network Pharmacology and Experimental Validation of Qingwen Baidu Decoction Therapeutic Potential in COVID-19-related Lung Injury

Background and Purpose: Coronavirus disease 2019 (COVID-19) is a lifethreatening disease worldwide due to its high infection and serious outcomes resulting from acute lung injury. Qingwen Baidu decoction (QBD), a well-known herbal prescription, has shown significant efficacy in patients with Coronavirus disease 2019. Hence, this study aims to uncover the molecular mechanism of QBD in treating COVID-19-related lung injury. Methods: Traditional Chinese Medicine Systems Pharmacology database (TCMSP), DrugBanks database, and Chinese Knowledge Infrastructure Project (CNKI) were used to retrieve the active ingredients of QBD. Drug and disease targets were collected using UniProt and Online Mendelian Inheritance in Man databases (OMIM). The core targets of QBD for pneumonia were analyzed by the Protein-Protein Interaction Network (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) to reveal the underlying molecular mechanisms. The analysis of key targets using molecular docking and animal experiments was also validated. Results: A compound-direct-acting target network mainly containing 171 compounds and 110 corresponding direct targets was constructed. The key targets included STAT3, c-JUN, TNF-α, MAPK3, MAPK1, FOS, PPARG, MAPK8, IFNG, NFκB1, etc. Moreover, 117 signaling pathways mainly involved in cytokine storm, inflammatory response, immune stress, oxidative stress and glucose metabolism were found by KEGG. The molecular docking results showed that the quercetin, alanine, and kaempferol in QBD demonstrated the strongest affinity to STAT3, c- JUN, and TNF-α. Experimental results displayed that QBD could effectively reduce the pathological damage to lung tissue by LPS and significantly alleviate the expression levels of the three key targets, thus playing a potential therapeutic role in COVID-19. Conclusion: QBD might be a promising therapeutic agent for COVID-19 via ameliorating STAT3-related signals.

Benzyl-isoquinoline alkaloids rich extract of Coptis teeta Wall., exhibit potential efficacy in calcium-oxalate and uric-acid linked metabolic disorders

Coptis teeta Wall., an endangered but valuable medicinal species having various folklore uses in Indian and Chinese Traditional system of medicine. Its distribution is restricted to India, China and Tibet. In India, C. teeta is traditionally used in joint disorders, urinary infections and inflammatory diseases, however the scientific validation is missing. Thus, the present study aims to validate the anti-lithiatic and anti-gout activity of C. teeta rhizome extract (CTME) through in-vitro biological assays. The metabolic fingerprinting of CTME through reverse phase-high performance liquid chromatography-photodiode array (RP-HPLC-PDA) showed the presence of five benzyl-isoquinoline alkaloids, namely berberine (2.59%), coptisine (0.746%) jatrorrhizine (0.133%), palmatine (0.03%) and tetrahydropalmatine (0.003%). The anti-gout potency analysed via in-vitro xanthine oxidase (XOD) inhibition assay, followed by HPTLC (High performance thin layer chromatography) mediated bio-autographic inhibition of XOD signifies that CTME exhibit strong inhibition of XOD (IC50: 3.014 μg/ml), insignificantly different (p > 0.05) from allopurinol (IC50: 2.47 μg/ml). The XOD bioautographic assay advocates that the efficacy is primarily due to berberine and coptisine alkaloids. The CTME has significant anti-lithiatic activity, and thereby limiting the progression of crystal nidus formation, mediated via inhibition of calcium oxalate crystals nucleation and aggregation. Additionally, the extract also exhibits potential effect on inhibition of oxidative stress associated inflammation, which plays crucial role in alleviating urolithiasis and gouty conditions. Validating the traditional claims of C. teeta will not only confirm its medicinal benefits for targeted pathological conditions but also enhance its industrial demand.

Exploring active ingredients and mechanisms of Coptidis Rhizoma-ginger against colon cancer using network pharmacology and molecular docking.

Colon cancer is the most prevalent and rapidly increasing malignancy globally. It has been suggested that some of the ingredients in the herb pair of Coptidis Rhizoma and ginger (Zingiber officinale), a traditional Chinese medicine, have potential anti-colon cancer properties. This study aimed to investigate the molecular mechanisms underlying the effects of the Coptidis Rhizoma-ginger herb pair in treating colon cancer, using an integrated approach combining network pharmacology and molecular docking. The ingredients of the herb pair Coptidis Rhizoma-ginger, along with their corresponding protein targets, were obtained from the Traditional Chinese Medicine System Pharmacology and Swiss Target Prediction databases. Target genes associated with colon cancer were retrieved from the GeneCards and OMIM databases. Then, the protein targets of the active ingredients in the herb pair were identified, and the disease-related overlapping targets were determined using the Venn online tool. The protein-protein interaction (PPI) network was constructed using STRING database and analyzed using Cytoscape 3.9.1 to identify key targets. Then, a compound-target-disease-pathway network map was constructed. The intersecting target genes were subjected to Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for colon cancer treatment. Molecular docking was performed using the Molecular Operating Environment (MOE) software to predict the binding affinity between the key targets and active compounds. Besides 1922 disease-related targets, 630 targets associated with 20 potential active compounds of the herb pair Coptidis Rhizoma-ginger were collected. Of these, 229 intersection targets were obtained. Forty key targets, including STAT3, Akt1, SRC, and HSP90AA1, were further analyzed using the ClueGO plugin in Cytoscape. These targets are involved in biological processes such as miRNA-mediated gene silencing, phosphatidylinositol 3-kinase (PI3K) signaling, and telomerase activity. KEGG enrichment analysis showed that PI3K-Akt and hypoxia-inducible factor 1 (HIF-1) signaling pathways were closely related to colon cancer prevention by the herb pair Coptidis Rhizoma-ginger. Ten genes (Akt1, TP53, STAT3, SRC, HSP90AA1, JAK2, CASP3, PTGS2, BCl2, and ESR1) were identified as key genes for validation through molecular docking simulation. This study demonstrated that the herb pair Coptidis Rhizoma-ginger exerted preventive effects against colon cancer by targeting multiple genes, utilizing various active compounds, and modulating multiple pathways. These findings might provide the basis for further investigations into the molecular mechanisms underlying the therapeutic effects of Coptidis Rhizoma-ginger in colon cancer treatment, potentially leading to the development of novel drugs for combating this disease.

Natural Compounds that Modulate Circadian Rhythms.

Circadian rhythms of innate 24 h cycles comprise well-conserved biological phenomena from cyanobacteria to mammalian. They are driven by light and regulated by clock genes that work as transcription factors and control the expression of many other genes and physiological functions in the cells. The expression of ~ 40% of protein-coding genes shows 24 h oscillation patterns in mice, implying their importance in normal body functions. Indeed, the physiological and behavioural rhythmicity generated through clock genes-mediated multiple mechanisms affects the quality of life at large. Disrupted circadian rhythmicity is associated with several kinds of diseases. For example, cancer cells show abnormal expression patterns for circadian rhythm genes that have been shown to regulate oncogenesis, drug responses, and disease prognosis. Furthermore, the modern globalisation of human lifestyle and business and social activities have disrupted innate circadian rhythm, resulting in a variety of diseases through disrupted humoral, immunological, and neuronal pathways. Safe and sustainable modulation of circadian rhythm has become a prevalent need that warrants basic and interventional research, as well as clinical investigations. Although traditional systems of medicine suggest some natural compounds with circadian rhythmmodulating potential, most of these have not been validated in laboratory or clinical studies. Reliable read-outs of the effects of test compounds on circadian rhythmicity have been limited by the availability of live cell assays. We have, herein, provided an overview of living cell-embedded real- time reporter gene assays designed for screening compounds that modulate circadian rhythm, and discussed the potential of some natural compounds for circadian rhythm modulation as validated by cell-based assay systems, and their role in disease therapeutics.

Exploring the therapeutic potential of achyranthes aspera: A comprehensive review

Achyranthes aspera, commonly known as "Prickly Chaff Flower," is a medicinal plant extensively used in traditional medicine systems worldwide. This review provides a comprehensive overview of the phytochemical constituents, pharmacological properties, and therapeutic potential of Achyranthes aspera. The phytochemical analysis reveals the presence of various bioactive compounds such as alkaloids, flavonoids, saponins, and terpenoids, among others, which contribute to its medicinal properties. Pharmacological studies have demonstrated the diverse therapeutic effects of Achyranthes aspera, including anti-inflammatory, analgesic, antioxidant, antimicrobial, antidiabetic, hepatoprotective, and anticancer activities. Furthermore, the plant has been utilized in the management of various ailments such as arthritis, diabetes, respiratory disorders, gastrointestinal disorders, and skin diseases. However, despite its promising therapeutic potential, further research is warranted to elucidate the underlying mechanisms of action and evaluate its safety and efficacy for clinical applications. This review aims to consolidate the existing knowledge on Achyranthes aspera, providing insights for future research and potential development of novel therapeutic agents.

Characteristics and comparative study of medicinal materials between China and India based on data mining from literatures

Ethnopharmacological relevanceChina and India have unique traditional medicine systems with vast territory and rich medical resources. Traditional medicines in China include traditional Chinese medicine, Tibetan medicine, Mongolian medicine, Uyghur medicine, Dai medicine, etc. In the third national survey of Chinese medicine resources, 12694 medicinal materials were identified. Traditional medicines in India include Ayurveda, Unani, Siddha, Homoeopathy, etc. There are 7263 medicinal materials in India. Aim of the studyTo reveal the characteristics of medicinal materials between China and India respectively, and to compare the similarities and differences in terms of properties, tastes, medicinal parts and therapeutic uses and to promote the exchange of traditional medicine between China and India and the international trade of traditional medicine industry. MethodsThe information of medicinal materials between China and India was extracted from The Chinese Traditional Medicine Resource Records and Pharmacopoeia of the People's Republic of China, as well as from 71 Indian herbal monographs. The information of each medicinal material, such as types, families, genera, properties, distribution, medicinal parts, efficacy, therapeutic uses, dosage form and dosage, was recorded in Excel for statistical analysis and visual comparison. ResultsA total of 12694 medicinal materials in China and 5362 medicinal materials in India were identified. The medicinal materials were mostly distributed in Southwest China and northern India. Plants were the main sources of medicinal materials. The common medicinal parts in China were whole medicinal materials, roots and rhizomes, and India used more renewable fruits, seeds and leaves. They are commonly used in the treatment of digestive system diseases. There were 1048 medicinal materials used by both China and India, which were distributed in 188 families and 685 genera. The Chinese and Indian pharmacopoeias had a total of 80 species of medicinal materials used by both China and India. ConclusionsThe characteristics of medicinal materials between China and India were somewhat different, which was conducive to provide a reference basis for traditional medicine in China or India to increase the medicinal parts and indications when using a certain medicinal material, as well as to expand the source of medicine and introduce new resources. However, there were certain similarities and shared medicinal materials, which can tap the potential of bilateral trade of medicinal materials between China and India, so as to promote the medical cultural exchange and economic and trade cooperation between the two countries.

Real-time Assessment of Ride-through Capability of Grid-tied Converter in Renewable Power Applications

This paper presents a comprehensive strategy for controlling grid-tied converters, with the primary goal of seamlessly integrating renewable power sources into the grid while ensuring stability and reliability. The control strategy is designed to achieve unity power factor operation under normal grid conditions, while also adhering to ride-through requirements to withstand voltage dips. Using the Typhoon HIL604 real-time simulation platform, extensive testing of the grid-tied converter is conducted to validate its performance. The results of the performance assessment are thoroughly analyzed and presented to exemplify the efficacy of the proposed control strategy. Notably, the paper emphasizes the converter's operation at unity power factor during normal grid conditions, indicating maximized active power delivery to the grid. Furthermore, the grid-tied converter demonstrates impressive ride-through capability during symmetrical voltage dip, achieved through the dynamic adjustment of grid current references to maintain grid stability. This research contributes to the advancement of grid-tied converter control strategies, offering insights into enhancing the integration of renewable power sources into the power grid while upholding system reliability and stability. Overall, this research offers valuable insights into the practical implementation of grid-tied converters for renewable power integration. It presents a comprehensive control strategy that not only enhances the integration of renewable power sources into the power grid but also prioritizes system reliability and stability.

Mechanism of Cnidii Fructus in the Treatment of Infertility Based on Network Pharmacology and Molecular Docking Analysis Technology.

Infertility is a condition characterized by a low fertility rate, which significantly affects the physical and mental health of women of reproductive age. Typically, the treatment duration is prolonged, and the therapeutic outcomes are often unsatisfactory. Professor Cheng-yao He, a renowned expert in traditional Chinese medicine, commonly uses the herb Cnidii Fructus (SCZ) for the treatment of infertility. However, the exact mechanism remains unclear, and there is limited research available on this topic. The active ingredients of SCZ were obtained from the traditional chinese medicine system pharmacology (TCMSP) database and screened for pharmacokinetics (PK), involving absorption, distribution, metabolism, and excretion (ADME). Target prediction was performed by SwissTargetPrediction database, and infertility-related disease targets were searched in GeneCards, TTD, DrugBank, and OMIM database. The protein-protein interaction (PPI) network was constructed using the STRING database (Version 11.5) and analyzed by Cytoscape software (Version 3.9.1). Additionally, the target genes were subjected to biological enrichment analysis in the Metascape database, including gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, and the "Disease-Ingredient-pathway-target" network was constructed using Cytoscape software. With the assistance of AutoDockVina, Ligplot, and PyMOL software, a validation of Molecular docking results and a visualization of the results were performed. This study identified 11 retained active ingredients of SCZ, 447 drug targets, 233 of which were related to infertility, and 5393 disease targets. GO enrichment analysis mainly involved 221 biological processes such as cellular response to chemical stress and gland development. KEGG enrichment analysis mainly involved 68 pathways such as thyroid hormone signaling pathway, estrogen signaling pathway, FOXO signaling pathway, and PI3K/Akt signaling pathway. Molecular docking showed that the core active ingredients of SCZ, including Ammidin, Diosmetin, Xanthoxylin N, and Prangenidin, had strong binding abilities with core targets such as MDM2, MTOR, CCND1, EGFR, and AKT1. This study preliminarily demonstrated that SCZ may act on the PI3K/Akt signaling pathway, exerting its therapeutic effects on infertility by improving energy metabolism disorders and endometrial receptivity, inducing primordial follicle activation, regulating oocyte proliferation, differentiation, and apoptosis, and promoting the release of dominant follicles.

Pharmacognostic Study and Standardization of Leaves and Stem of Mentha spicata Linn.

Background:: Various Mentha species are cultivated all over the world due to their aroma and valuable therapeutic constituents. Along with its traditional use as a food flavor, it is well-established folklore medicine for treating digestive and cardiovascular problems. Mentha spicata L. is a perennial, aromatic herb belonging to the Lamiaceae family. M. spicata leaves have been used in traditional systems of medicines for treating various digestive system disorders since old times. Aim:: The present research work encompasses the pharmacognostic study, phytochemical screening and physicochemical parameter estimation of leaves and stem of M. spicata L. for standardization of Mentha plant. Materials and Methods:: Morpho-anatomical characterization, physicochemical analysis and preliminary phytochemical investigation of leaves and stems were performed. These investigations were done as per WHO guidelines to determine the main diagnostic characteristics for correct identification and standardization of whole plant and powdered drug of M. spicata L. Results:: The dimensions, size, color, and surface texture characteristics of fresh crude drug (leaf and stem) were determined. Compound microscope images of the transverse section (TS) of M. spicata leaf and stem revealed the cellular arrangement and main identification characters. Phytochemical and physicochemical analysis of powdered drugs confirmed the presence of important phytoconstituents such as phytosterol, terpeneoids, phenolic compounds, saponins, volatile oil, etc. Conclusion:: The results obtained are helpful for the characterization of the crude drug. Morphoanatomical characterization and physicochemical analysis are inexpensive methods and serve as a quality control tool for stem and leaf standardization. The ethanolic and aqueous extract of leaves and stem showed the presence of valuable medicinally active phytoconstituents.

Network pharmacology and transcriptomics analysis reveal the mechanism of BushenHuoxue formula attenuates premature ovarian failure via modulation PI3K/AKT pathway.

This study aims to analyze the active components and mechanism of Bushen Huoxue (BSHX) formula on the autoimmune premature ovarian insufficiency (POI) by combining network pharmacology and Transcriptomics. The active components and targets of BSHXF were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). POI-related targets were identified through Therapeutic Targets Database (TTD), DisGeNET and drugbank database. The Veen diagram was performed to obtain the action targets. The active compound-target network and Protein-Protein Interaction (PPI) network were built by using STRING database and Cytoscape software. Key targets and active compounds were further identified by topological analysis. Molecular docking shows that Kaempferol, Isorhamnetin and Anhydroicaritin have strong binding to AKT. Finally, a zp3-induced autoimmune ovarian function deficiency mouse model was used to explore the potential mechanism of POI. The potential pathways of BSHXF for the treatment of POI were identified by Transcriptomic analysis. PI3K-AKT and NF-kb pathways were the common pathways between network pharmacology and transcriptomics. Our results revealed that BSHXF could reduce the FSH expression levels and raise the E2, and AMH levels in the serum. Western bloting demonstrates that BSHXF could upregulate the expression of p-PI3K and p-AKT.

Activation of GABA type A receptor is involved in the anti-insomnia effect of Huanglian Wendan Decoction

Huanglian Wendan Decoction (HWD) is a traditional Chinese medicine (TCM) prescribed to patients diagnosed with insomnia, which can achieve excellent therapeutic outcomes. As positively modulating the γ-aminobutyric acid (GABA) type A receptors (GABAARs) is the most effective strategy to manage insomnia, this study aimed to investigate whether the activation of GABAARs is involved in the anti-insomnia effect of HWD. We assessed the metabolites of HWD using LC/MS and the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and tested the pharmacological activity in vitro and in vivo using whole-cell patch clamp and insomnia zebrafish model. In HEK293 cells expressing α1β3γ2L GABAARs, HWD effectively increased the GABA-induced currents and could induce GABAAR-mediated currents independent of the application of GABA. In the LC-MS (QToF) assay, 31 metabolites were discovered in negative ion modes and 37 metabolites were found in positive ion modes, but neither three selected active metabolites, Danshensu, Coptisine, or Dihydromyricetin, showed potentiating effects on GABA currents. 62 active metabolites of the seven botanical drugs were collected based on the TCMSP database and 19 of them were selected for patch-clamp verification according to the virtual docking simulations and other parameters. At a concentration of 100 μM, GABA-induced currents were increased by (+)-Cuparene (278.80% ± 19.13%), Ethyl glucoside (225.40% ± 21.77%), and β-Caryophyllene (290.11% ± 17.71%). In addition, (+)-Cuparene, Ethyl glucoside, and β-Caryophyllene could also serve as positive allosteric modulators (PAMs) and shifted the GABA dose-response curve (DRC) leftward significantly. In the PCPA-induced zebrafish model, Ethyl glucoside showed anti-insomnia effects at concentrations of 100 μM. In this research, we demonstrated that the activation of GABAARs was involved in the anti-insomnia effect of HWD, and Ethyl glucoside might be a key metabolite in treating insomnia.

Widely targeted metabolomics analysis of Sanghuangporus vaninii mycelia and fruiting bodies at different harvest stages

Sanghuangprous vaninii is a medicinal macrofungus cultivated extensively in China. Both the mycelia and fruiting bodies of S. vaninii have remarkable therapeutic properties, but it remains unclear whether the mycelia may serve as a substitute for the fruiting bodies. Furthermore, S. vaninii is a perennial fungus with therapeutic components that vary significantly depending on the growing year of the fruiting bodies. Hence, it is critical to select an appropriate harvest stage for S. vaninii fruiting bodies for a specific purpose. With the aid of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), metabolomics based on ultra-high performance liquid chromatography coupled to triple quadrupole mass spectrometry (UHPLC-QQQ-MS) was used to preliminarily determine 81 key active metabolites and 157 active pharmaceutical metabolites in S. vaninii responsible for resistance to the six major diseases. To evaluate the substitutability of the mycelia and fruiting bodies of S. vaninii and to select an appropriate harvest stage for the fruiting bodies of S. vaninii, we analyzed the metabolite differences, especially active metabolite differences, among the mycelia and fruiting bodies during three different harvest stages (1-year-old, 2-year-old, and 3-year-old). Moreover, we also determined the most prominent and crucial metabolites in each sample of S. vaninii. These results suggested that the mycelia show promise as a substitute for the fruiting bodies of S. vaninii and that extending the growth year does not necessarily lead to higher accumulation levels of active metabolites in the S. vaninii fruiting bodies. This study provided a theoretical basis for developing and using S. vaninii.

Qualitative and quantitative metabolomics of Pamburus missionis Swingle – a medicinal tree taxon

Since ancient times, Plant based medicine is a well-known oldest form of healthcare to mankind. Even the commercial medications used for the treatment of various ailments today, contains a large proportion of plant derived chemical compounds. Hence chemical profiling of medicinal plants gained a key role to use them in pharmaceuticals as well as commercial industries. Pamburus missionis is one of the medicinal plants used in the Indian and Srilankan traditional medicine system to reduce kapha dosha. The ayurvedic physicians used its leaves to treat swelling, piles, fractures, fistula, puerperal diseases and as serpent venom. Therefore, the present study was undertaken to reveal the phytocompounds from various parts of this plant. Metabolomics revealed the presence of primary and secondary metabolites like carbohydrates, lipids, proteins, alkaloids, phenols, flavonoids, steroids etc. From the aqueous extract, Alkaloid content is almost same in leaf, stem and bark extracts with around 1.2 to 1.3 g (w/v%) and completely absent in the fruit. Phenolic content and steroids are notably high in leaf extract with 112.77±0.34 mg/g of extract and 17.91±0.26 mg respectively, where the flavonoid content in fruit extract with 44.69±0.30 mg/g of extract and the tannin content in bark extract with 62.37±1.75 mg/g of extract.

Neoergosterol-rich mushroom extract, resourced from wild edible mushroom Termitomyces heimii Natarajan, induces robust apoptosis against lung cancer

The non-specificity of conventional cancer drugs imposes a significant obstacle in cancer treatment, so the development of a safe anti-cancer alternative by methodologically revisiting several traditional medicinal systems may be a possible way to get rid of this problem. Therefore, the present study evaluates the anti-cancer potentiality of one of the Asiatic and African regions’ widely popular edible and ethnobotanically significant termite mushroom, Termitomyces heimii Natarajan (T. heimii), against various cancers. The anti-proliferative and chemo-preventive potentiality of two different extracts of T. heimii was evaluated against a panel of eight cancer cell lines and normal cells through an MTT assay. In vitro screening highlights that the methanolic extract of T. heimii had the highest anti-proliferative potential against A549 cells and had a negligible effect on normal cells. The extract specifically induced robust apoptosis in A549 cells through augmentation of intracellular ROS, disrupting mitochondrial membrane polarity, thus ultimately resulting in caspase-dependent apoptosis in lung cancer cells. Post-treatment, down-regulation of anti-apoptotic BCL-2 coordinated up-regulation of BAX expression, and an elevated expression of p53 signified the p53-dependent apoptosis. Moreover, the mushroom extract restricted cellular migration in the palladin-dependent pathway by downregulating the expression of PALLADIN. LC-MS-based metabolomic profiling was conducted to identify the potential anti-cancer mycocompounds in the methanol extract. The metabolomic profiling analysis, followed by an in silico molecular docking study, identified a unique mycosterol, neoergosterol, as a possible anti-cancer compound in the mushroom extract. The present study concludes a novel mycocompound neoergosterol resourcing from Termitomyces heimii Natarajan, demonstrating selective robust apoptosis against non-small cell lung cancer cells and also provides a chemoprotective shield against normal cells, which holds great promise for future drug development to treat lung cancer.

Ji-Ni-De-Xie ameliorates type 2 diabetes mellitus by modulating the bile acids metabolism and FXR/FGF15 signaling pathway.

Introduction: Ji-Ni-De-Xie (JNDX) is a traditional herbal preparation in China. It is widely used to treat type 2 diabetes mellitus (T2DM) in traditional Tibetan medicine system. However, its antidiabetic mechanisms have not been elucidated. The aim of this study is to elucidate the underlying mechanism of JNDX on bile acids (BAs) metabolism and FXR/FGF15 signaling pathway in T2DM rats. Methods: High-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-QQQ-MS) and UPLC-Q-Exactive Orbitrap MS technology were used to identify the constituents in JNDX. High-fat diet (HFD) combined with streptozotocin (45 mg∙kg-1) (STZ) was used to establish a T2DM rat model, and the levels of fasting blood-glucose (FBG), glycosylated serum protein (GSP), homeostasis model assessment of insulin resistance (HOMA-IR), LPS, TNF-α, IL-1β, IL-6, TG, TC, LDL-C, HDL-C, and insulin sensitivity index (ISI) were measured to evaluate the anti-diabetic activity of JNDX. In addition, metagenomic analysis was performed to detect changes in gut microbiota. The metabolic profile of BAs was analyzed by HPLC-QQQ-MS. Moreover, the protein and mRNA expressions of FXR and FGF15 in the colon and the protein expressions of FGF15 and CYP7A1 in the liver of T2DM rats were measured by western blot and RT-qPCR. Results: A total of 12 constituents were identified by HPLC-QQQ-MS in JNDX. Furthermore, 45 chemical components in serum were identified from JNDX via UPLC-Q-Exactive Orbitrap MS technology, including 22 prototype components and 23 metabolites. Using a T2DM rat model, we found that JNDX (0.083, 0.165 and 0.33 g/kg) reduced the levels of FBG, GSP, HOMA-IR, LPS, TNF-α, IL-1β, IL-6, TG, TC, and LDL-C, and increased ISI and HDL-C levels in T2DM rats. Metagenomic results demonstrated that JNDX treatment effectively improved gut microbiota dysbiosis, including altering some bacteria (e.g., Streptococcus and Bacteroides) associated with BAs metabolism. Additionally, JNDX improved BAs disorder in T2DM rats, especially significantly increasing cholic acid (CA) levels and decreasing ursodeoxycholic acid (UDCA) levels. Moreover, the protein and mRNA expressions of FXR and FGF15 of T2DM rats were significantly increased, while the expression of CYP7A1 protein in the liver was markedly inhibited by JNDX. Discussion: JNDX can effectively improve insulin resistance, hyperglycemia, hyperlipidemia, and inflammation in T2DM rats. The mechanism is related to its regulation of BAs metabolism and activation of FXR/FGF15 signaling pathway.