Tibetan Medicine Research Articles

Effect of a Tibetan Medicine Rinqingchangjue on Gastric Hypomotility in Rats

Effect of a Tibetan Medicine Rinqingchangjue on Gastric Hypomotility in Rats

Interactive Nutrient Process (INP) in a Generative AI of a New Drug-6-Shogaol as a Potential Case.

The dynamically evolving science of pharmacology requires AI technology to advance a new path for drug development. The author proposes generative AI for future drugs, identifying suitable drug molecules, uncharacteristically to previous generations of medicines, incorporating the wisdom, experience, and intuit of traditional materia medica and the respective traditional medicine practitioners. This paper describes the guiding principles of the new drug development, springing from the tradition and practice of Tibetan medicine, defined as the Interactive Nutrient Process (INP). The INP provides traditional knowledge and practitioner's experience, contextualizing and teaching the new drug therapy. An illustrative example of the outcome of the INP is a potential small molecule drug, 6-Shogaol and related shogaol derivatives, from ginger roots (Zingiber officinalis fam. Zingiberaceae) evaluated clinically for 12 months for biological markers of iron homeostasis in patients with the myelodysplastic syndromes (MDS). The study's preliminary results indicate that 6-Shogaol and related shogaols may improve iron homeostasis in low-risk/intermediate-1 MDS patients without objective or subjective side effects.

Research Progress on Tibetan Medicine for the Treatment of Tuberculosis

Research Progress on Tibetan Medicine for the Treatment of Tuberculosis

Tibetan medicine Ruyi Zhenbao Pill ameliorates neuropathic pain by inhibiting the CXCL10-CXCR3 pathway in spinal cord of spinal nerve ligation model

Ethnopharmacological relevanceRuyi Zhenbao Pill (RYZBP) is a traditional Tibetan medicine that has been used for over 300 years in China to treat neurological diseases, specifically neuropathic pain (NP). However, its characteristics and mechanism of action in treating NP remains unclear. Aim of the studyBased on animal experiments and transcriptomics to evaluate the characteristics and mechanism of RYZBP in treating NP. MethodsMice were divided into six groups using random assignment: sham-operation group, spinal nerve ligation (SNL) group, RYZBP low (0.65 g kg−1), medium (1.30 g kg−1), high (2.60 g kg−1) doses groups, and positive drug pregabalin (PGB, 0.05 g kg−1) group. Mice received intragastrical administered for 14 consecutive days. SNL and intrathecal injection models were employed. The analgesic effects were assessed using the Von Frey test, Acetone test, and Hot Plate test. L5 spinal dorsal horns were collected for transcriptomics on day 15. The potential signaling pathways and Hub genes of RYZBP to ameliorate NP were obtained through transcriptomics and network pharmacology. Molecular docking was utilized to evaluate the binding ability of candidate active ingredients with the Hub genes. Finally, western blot (WB) and immunofluorescence (IF) were used to validate the predicted targets. ResultsRYZBP demonstrated a dose-dependent alleviation of mechanical allodynia, cold and heat stimulus-induced pain in SNL mice. Transcriptomics analysis identified 24 differentially expressed genes, and pathway enrichment analysis revealed that the CXCL10-CXCR3 signal axis may be the primary biological pathway through which RYZBP relieve NP. Molecular docking test indicated that the active ingredient in RYZBP exhibit a strong affinity for the target protein CXCL10. WB and IF tests showed that RYZBP can significantly inhibit CXCL10 and CXCR3 and its downstream molecules expression in the spinal dorsal horn of SNL mice. Additionally, intrathecal injection of rmCXCL10 worsened pain hypersensitivity, while RYZBP was able to suppress the pain hypersensitivity response induced by rmCXCL10 and reduce the expression levels of CXCL10 and CXCR3 and its downstream molecules. ConclusionRYZBP had a significant analgesic effect on NP model, and this effect may be related to inhibiting the CXCL10-CXCR3 pathway in the spinal dorsal horn.

«Сотворение тела» в тибетском трактате «Чжуд-ши»

Introduction. The fundamental Buddhist treatise rGyud-bZhi is compiled mainly from Indian and Chinese sources, as well as elements of the oral healing tradition. The extensive range of commentary texts rGyud-bZhi gave rise to is dominated by the treatise Vaidurya-Onbo containing a series of unique illustrations — the ‘Atlas of Tibetan Medicine’. Tibetan healers considered embryology a most important part of medical practice and described it as the ‘making of the body’. Goals. The study seeks to consider the phenomenon of the making of the body — covering the pre-conception period, process of conception, fetal development, birth, postnatal growth, and infancy — in the context of the Buddhist healing treatise rGyud-bZhi and related commentaries. The paper examines conditions and causes of conception, processes of embryonic development, sex determination, karma-based birth to a certain family. Materials and methods. The work analyzes the embryology on the basis of rGyud-bZhi and Vaidurya-Onbo with the illustrations referred to as ‘Atlas of Tibetan Medicine’. One of the most impressive illustrations of the Atlas is titled ‘The Making of the Body’, and explains how under the influence of the vijñāna (‘consciousness’), the five primary elements and attachment to samsara, conception occurs and the fetus gets formed. Results. The making of the body is determined by karma and begins long before the embryo’s conception, since Buddhist texts pay much attention to the moral behavior of would-be parents. In Tibetan society, the influence of traditions manifested itself already at the stage of embryonic development, and women would often turn to mystical rites and rituals in the hope of giving birth to a male child. It was believed that prayers and certain rituals could influence the formation of the unborn child’s sex. Childbirth is basically viewed as a positive event for woman, since it is biologically and culturally natural. According to Tibetan sources, human health is rooted in harmony with environments and moral principles. Parents understand that it is necessary to follow internal and external prescriptions for procreation, to increase physical and spiritual strength in order to successfully conceive, maintain pregnancy, give birth to a healthy child and provide him/her with proper care.

Sequence Analysis of the Plastomes of Two Tibetan Medicinal Plants of the Family Papaveraceae.

With the rapid development of next-generation sequencing technology, more plants plastomes have been sequenced, further advancing species identification and phylogenetic studies. However, there are a few studies on the genetic and phylogenetic analysis of the plastomes of Dicranostigma lactucoides Hook. f. et Thoms. and Hypecoum leptocarpum Hook. f. et Thoms. In this study, we sequenced and analyzed the plastomes of Dicranostigma lactucoides Hook. f. et Thoms. and Hypecoum leptocarpum Hook. f. et Thoms., and conducted a phylogenetic analysis using 13 related species. The results showed that the plastomes of both D. lactucoides and H. leptocarpum had a typical tetrad structure, with sizes of 166,819 bp and 163,282 bp, respectively. We annotated 133 genes for D. lactucoides and 120 genes for H. leptocarpum. A total of 72 and 43 simple repetitive sequences were detected in D. lactucoides and H. leptocarpum, respectively. Codon preference analysis showed that the relative usage frequency of codons and the relative abundance of synonymous codons used were the same for both plastomes. Nucleotide polymorphism analysis identified seven variant loci with high nucleotide diversity (Pi) values, all located in the large single copy (LSC) region. Inverted repeat (IR) boundary analysis revealed differences in gene types and locations on both sides of the boundary, except for the small single copy/inverted repeat a (SSC/IRa) boundary. The phylogenetic analysis showed the species clustered into two major groups, one with five genera (Hypecoum, Corydalis, Papaver, Meconopsis, and Dicranostigma) and the other with two genera (Coreanomecon; and Hylomecon). Comparative analysis of the plastome genomic characteristics and phylogeny of D. lactucoides and H. leptocarpum laid the foundation for identifying the above two species and the phylogenetic study and comprehensive exploitation of the Papaveraceae.

Deciphering the mysteries of Aconitum pendulum: Unique identification of various processed products and characteristic chemical markers

Aconitum pendulum, a member of the Aconitum genus within the Ranunculaceae family, is known for its remarkable anti-inflammatory, anti-tumor, and analgesic properties. However, the application of Aconitum pendulum in traditional medicine is often restricted by its inherent toxicity, necessitating specific processing methods to ensure safe usage. Tibetan medicine utilizes distinctive processing techniques such as the barley wine, Hezitang, and zanba frying systems to render the herb safe for medicinal use. Despite the known pharmacological importance, scant research exists on how these processing methods affect the phytochemical profile of Aconitum pendulum, indicating a necessity for comparative analysis of the resulting concoctions. In this study, we employed 1H nuclear magnetic resonance (1H NMR) spectroscopy and ultra-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) to explore the metabolomic variations among different processed products of Aconitum pendulum. Multivariate data analysis techniques, including pattern recognition, allowed us to investigate the intricacies of the compound profiles. To discover signature chemical markers that can differentiate the various processed products, we conducted paired t-tests and generated heat maps highlighting the detected differences. Our integrated analysis of the 1H NMR and UPLC-Q-TOF-MS data revealed distinct chemical signatures unique to each method of Aconitum pendulum processing. By employing chemometric analysis with variable importance in projection (VIP) scores greater than 1.0, and coupled with the statistical rigor of paired t-tests (P < 0.05), we successfully identified significant chemical markers in various processed products, including ferulic acid (FA), caffeic acid (CA), 3-acetylaconitine (AAC) and benzoylaconitine (BAC). Our findings provide a rapid and robust analysis of the chemical constituencies within raw and processed Aconitum pendulum. The discovery of potential chemical markers through an array of advanced pattern recognition techniques offers a substantial contribution to the pharmaceutical analysis. The results of this research pave the way for future comparative studies and facilitate the recognition of distinctively processed Aconitum pendulum products in traditional medicine.

Separation of Antioxidants from Trace Fraction of Ribes himalense via Chromatographic Strategy and Their Antioxidant Activity Supported with Molecular Simulations.

Antioxidants from natural sources have long been of interest to researchers. In this paper, taking the traditional Tibetan medicine Ribes himalense as an example, an integrated approach was used to identify and isolate its chemical composition with free-radical-scavenging properties from its ethanol extract. First, the ethanol extract of Ribes himalense was pretreated using polyamide medium-pressure liquid chromatography (polyamide-MPLC), and the target fraction (Fr4) was obtained. Then, a combined HPLC mode was utilized to purify antioxidants in Fr4 under the guidance of an online HPLC-1,1-diphenyl-2-picrylhydrazyl (HPLC-DPPH) activity screening system. Finally, three antioxidants (3-caffeoylquinic acid methyl ester, rutin, and myricetin-3'-α-L-rhamnopyranoside) were isolated, and this is the first report of their presence in R. himalense. Further molecular docking studies showed that the antioxidants exhibited good binding with HO-1, Nrf2, and iNOS. In conclusion, this comprehensive approach is capable of extracting high-purity antioxidants from trace fractions of Ribes himalense and holds promise for future applications in the exploration of the chemical compositions and bioactivity of natural products.

A core root bacteria contribute to plant growth and anisodine accumulation of Anisodus tanguticus

BackgroundAlthough it is well recognized that core root microorganisms contribute to plant health and productivity, little is known about their role to the accumulation of secondary metabolites. The roots of Anisodus tanguticus, a traditional herbal medication utilized by Tibetan medicine, are rich in tropane alkaloids. We collected wild A. tanguticus populations throughout a 1500 km transect on the Qinghai-Tibetan Plateau.ResultsOur results showed that despite sampling at a distance of 1500 km, the root of A. tanguticus selectively recruits core root bacteria. We obtained 102 root bacterial core OTUs, and although their number only accounted for 2.99% of the total, their relative abundance accounted for 73% of the total. Spearman correlation and random forest analyses revealed that the composition of core root microbiomes was related to anisodine contents, aboveground biomass and nitrogen contents of Anisodus tanguticus. Among them, the main role is played by Rhizobacter, Variovorax, Polaromonas, and Mycobacterium genus that are significantly enriched in roots. Functional prediction by FAPROTAX showed that nitrogen-cycling microorganisms and pathogenic bacteria are strongly associated with anisodine contents, aboveground biomass and nitrogen contents of Anisodus tanguticus.ConclusionsOur findings show that the root selectively recruits core root bacteria and revealed that the core microbiomes and microbial functions potentially contributed to the anisodine contents, aboveground biomass and nitrogen contents of the plant. This work may increase our understanding of the interactions between microorganisms and plants and improve our ability to manage root microbiota to promote sustainable production of herbal medicines.

A comprehensive review of Shengdeng in Tibetan medicine: textual research, herbal and botanical distribution, traditional uses, phytochemistry, and pharmacology.

"Shengdeng", a group of Tibetan medicines with diverse biological origins, has long been utilized in Tibet for the treatment of rheumatoid arthritis. It showcases remarkable efficacy in alleviating rheumatism, reducing swelling, and relieving pain. This study aimed to clarify the plant species used as "Shengdeng" and summarize their botanical distribution, traditional uses, phytochemistry, and pharmacology to promote its utilization and development. "Shengdeng" is derived from a remarkable collection of 14 plant species belonging to six distinct families. Extensive phytochemical investigations have led to the identification of 355 chemical constituents within "Shengdeng". Pharmacological studies conducted on "Shengdeng" have revealed a wide range of beneficial properties, including antioxidant, anticancer, antimicrobial, antiviral, antiparasitic, anti-inflammatory, and anti-arthritic activities. Notably, flavonoids and triterpenoids emerge as the predominant groups among these constituents, contributing to the therapeutic potential and diverse applications of "Shengdeng". The present review provides a concise summary of the recent advancements in textual research concerning the herbal and botanical distribution, traditional uses, phytochemistry, and pharmacological activities of "Shengdeng". It is crucial to note that future research on "Shengdeng" should prioritize the analysis of its active ingredients and the establishment of rigorous quality standards. These aspects are essential for ensuring consistency, efficacy, and safety in its clinical application.

Tibetan medicine Bang Jian: a comprehensive review on botanical characterization, traditional use, phytochemistry, and pharmacology.

Tibetan medicine Bang Jian refers to a range of botanical drugs within the Gentiana genus. It serves as a prominent traditional Tibetan botanical drug primarily found in the ethnic minority regions of the Qinghai-Tibet Plateau in China. Traditionally, the dried flowers of Bang Jian, known as "Longdanhua" have been employed in Tibetan medicine to address detoxification, pharyngeal relief, acute and chronic bronchitis, bronchiectasis, lung infections, pulmonary fibrosis, and throat disorders. Surprisingly, there has been no comprehensive review published to date on Tibetan medicine Bang Jian. This passage systematically presents and critically assesses recent advancements in botanical characterization, traditional applications, phytochemistry, pharmacology, and clinical uses of Bang Jian, aiming to provide a scientific foundation for its reasonable use and further exploration. To date, researchers have isolated and identified 92 structurally diverse compounds, with a predominant presence of iridoids, flavonoids, xanthones, and triterpenoids. The crude extracts and metabolites derived from Bang Jian have been found to exhibit a wide range of pharmacological effects, encompassing anti-inflammatory, anti-tumor, anti-bacterial, antiviral, antioxidant, hepatoprotective properties, and protect the respiratory system. Nevertheless, detailed data on the biological effects, metabolic activities, and mechanistic research concerning active monomer metabolites remain insufficient. Consequently, there is a pressing need for comprehensive and in-depth research to guide rational clinical drug usage and evaluate the medicinal attributes of Bang Jian.

Traditional medicine of three regions of Russia and the use of information technologies to investigate it

The paper presents experience of investigating the traditional medicine for the three regions of Russia – Buryatia, Kalmykia and Tuva — that has been kind of folk tradition here for centuries. This is Tibetan medicine that is the cultural and historical heir of the Indian medical tradition using some elements of the Chinese medicine. The paper gives information on the problem of objectifying and automating the Tibetan diagnostic methods (inspection, palpation, questioning) using information technologies. This research has been carried out in two directions: objectification and automation of pulse diagnostics by the development of the Computer Pulse Diagnostic System and the development of the Expert Diagnostic System for questioning and inspection of a patient. On the basis of the assessments of the experts (specialists in pulse diagnostics) and mathematically detected diagnostic signs of pulse waves, statistical models of normal and pathological pulses (pulses of «hot» and «cold» diseases) have been developed. A catalogue of pulses is being compiled. This catalogue consists of classes of computer recorded pulse signals that correspond to Tibetan nosology. The expanded and differentiated catalog of pulses and the pulse wave pattern recognition program designed to compare measured pulses and reference pulses will make the basis for combining the diagnostic results by three diagnostic methods, which will lead to the creation of an Integral Computer Diagnostic System designed for diagnosing diseases and providing recommendations for health correction in accordance with the traditions of Tibetan medicine.

Can Tibetan medicine Honghua Ruyi pills relieve endometriosis-associated dysmenorrhea? Protocol for a randomized placebo-controlled trial

ObjectiveTo provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi (HHRY) pills for endometriosis-associated dysmenorrhea. MethodsThis study constitutes a multicenter, randomized, double-blind, placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period. A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 ratio. The primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale (VAS) scores and quality of life, whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain, duration of pain episodes (in days), frequency and quantity of the consumption of ibuprofen sustained-release capsules (or other non-steroidal anti-inflammatory drugs), and days off work/study for staff/student due to dysmenorrhea, ovarian cyst, and/or pelvic nodule size. The safety was monitored throughout the treatment period. All the analyses were based on the intention-to-treat principle. For continuous outcomes, simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups, with categorical data expressed as the number and percentage of occurrences. Differences were compared using the chi-square test or Fisher's exact test. The predefined analysis was adjusted for concomitant treatment, a variable considered to be associated with outcomes but unaffected by treatment allocation. Estimates of treatment effects were reported with 95% confidence intervals. Two-tailed P values ≤ .05 were considered statistically significant. ConclusionPositive results from this trial, upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

2D-HPLC-MS Technology Combined with Molecular Network for the Identification of Components in Tibetan medicine Aconitum pendulum.

In this study, a comprehensive approach was employed, utilizing 2D-HPLC-MS technology in conjunction with the molecular network to unravel the intricate chemical composition of the Tibetan medicinal plant APB. Through the implementation of 2D-HPLC, enhanced separation of complex mixtures was achieved, enabling the isolation of individual compounds for subsequent analysis. The molecular network approach further aided in elucidating structural relationships among these compounds, contributing to the determination of potential bioactive molecules. This integrated strategy efficiently identified a wide array of chemical components present within the plant. The findings revealed a diverse spectrum of chemical constituents within APB, including alkaloids, among others. This research not only advances understanding of the phytochemical profile of this traditional Tibetan medicine but also provides valuable insights into its potential therapeutic properties. The integration of 2D-HPLC-MS and molecular network proves to be a powerful tool for systematically exploring and identifying complex chemical compositions in herbal medicines, paving the way for further research and development in the field of natural product discovery.

Determination of the pharmacodynamic substances and mechanism of Shiwuwei Saierdou Pills against cholestatic hepatitis through chemical profile identification and network pharmacology analysis

Cholestatic hepatitis (CH) is a liver lesion caused by abnormal bile production, secretion and excretion and has a complex pathogenesis. The Tibetan medicine Shiwuwei Saierdou Pills (SSP) is an empirical Tibetan medicine formula for the treatment of CH, but its chemical composition is complex and the material basis of its efficacy is not yet clear. So, in this study, the main chemical constituents and its blood-incorporated constituents in SSP were analyzed by ultra-high-performance liquid chromatography-quadruple-electrostatic field orbitrap high resolution mass spectrometry (UHPLC-Q-Exactive Orbitrap/MS), Then, the blood-incorporated constituents were subjected to network pharmacology analysis to preliminarily clarify its potential pharmacological substances and mechanism. and further, it was verified through molecular docking and in vivo animal experiments. As a result, a total of 80 chemical components were identified in the SSP, of which 11 were confirmed by reference standards and 20 blood-incorporated constituents (including 10 prototypes and 10 metabolites) were characterized in the serum containing the medicine. The core targets of SSP for the treatment of CH were identified as AKT1, VEGFA, CASP3, SRC and MAPK3 through the screening of the relationship between the blood-incorporated constituents and the targets. Combined with the results of molecular docking, swertiamarin, ellagic acid, taurocholic acid and bellidifolin in the ten prototypes may be the key pharmacodynamic substances for SSP to treat CH. The results of animal experiments showed that SSP could significantly inhibit the pathological changes of the CH rat model, and inhibit the protein expression of AKT1, VEGFA, CASP3, SRC and MAPK3. In summary, we used network pharmacology, molecular docking and animal experiments to preliminarily determine the main medicinal components, targets and pathways of SSP in the treatment of CH, which provides a scientific basis for further revealing the material basis and mechanism of SSP in treating CH.

Cultivation, Phytochemical screening and Antimicrobial analysis of caterpillar mushroom Cordyceps militaris and fruiting body

The fungus Cordyceps militaris comes under the family cordyciptiaceae and class ascomycetes. In ancient time it was used in Chinese and Tibetan medicines for lungs and kidney diseases but with the change in era, more researches were conducted on it. This study was designed for the cultivation of Cordyceps militaris (C.M.) mushroom on brown rice media as the measure component and evaluation of its quantitative, qualitative and free radical scavenging activity of the methanolic extract. To know the bioactive compounds, preliminary phytochemical analysis was done which states that methanolic extract of Cordyceps contains protein, phenol, alkaloids, tannin, flavonoids, coumarins, polysaccharides and carbohydrates. The quantitative analysis of methanolic extract was quantified using determination of total phenol and total flavonoids using Folin-Ciocalteu reagent and Aluminium calorimetric assay method respectively. Phyto- compounds were depicted through Fourier transform infrared spectroscopy (FTIR) and Gas chromatography- mass spectroscopy (GC-MS) while the free radical scavenging activity was determined using the 1,1-diphenyl-2-pycryl-hydrazyl (DPPH) assay, hydrogen peroxide assay, ferric reducing antioxidant power (FRAP) assay and reducing power assay. Highest phenolic and flavonoid contents were depicted in CM100%meth while CM100%meth. showed highest free radical scavenging activity. The assessment of extract for antimicrobial activity was done with well diffusion method against Gram positive and Gram negative bacteria revealing that aqueous and methanolic extract are more effective against Bacillus subtilis and Escherichia coli.

An integrated strategy of UPLC-Q-TOF/MS and HPTLC/PAD-DESI-MSI for the analysis of chemical variations: A case study of Tibetan medicine Tiebangchui

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Tibetan mineral-herbal medicine Zuotai alleviates the depressive-like behaviors in chronic restraint-stressed mice while regulating stress hormone, inflammation and monoamine

Introduction:Zuotaiis an ancient mineral-herbal mixture containing β-HgS in Tibetan medicine. It is used to treat nervous system diseases, similar to Chinese medicine cinnabar and Indian Ayurveda medicineRasasindura. However, one of the key problems faced byZuotaiis that its indications are ambiguous. Our previous study found thatZuotaiexhibited the activity of ameliorating depressive-like behaviors in a chronic mild stress model. However, due to the inherent limitations of animal models in simulating human disease, clear results often require more than one model for confirmation.Methods:Therefore, another depression model, chronic restraint stressed (CRS) mice, was used to validate the antidepression effect ofZuotai. Prophylactic treatment was conducted for 21 consecutive days while mice were subjected to chronic restraint stress.Results:It was observed thatZuotaiand β-HgS alleviated anhedonia, behavioral despair, stereotype behavior, and reduced exploratory and spontaneous movement in CRS mice.Zuotaiand β-HgS also reversed the increases of stress hormone corticosterone (Cort) in serum and pro-inflammatory cytokines in serum and brain, and increased the serotonin in cortex in CRS mice, with positive dose-effect relationship. The number of Ki67-positive cells in the dentate gyrus and the level of brain-derived neurotrophic factor (BDNF) in the hippocampus were slightly elevated in CRS mice treated withZuotai; however, there was no statistically significant difference. AlthoughZuotaiincreased the total Hg concentration in main organs, the levels remained below those needed to result in observed adverse effect, at least for kidney and liver; andZuotaishowed no observed adverse effect on the brain histopathology, the cell proliferation in dentate gyrus, as well as the hippocampal and cortical organ coefficients.Conclusion:Zuotaiexhibited the alleviation of depressive-like behaviors in CRS mice, accompanying with ameliorating stress hormone, peripherical and cerebral inflammation, and monoamine neurotransmitter.

Gentiana macrophylla flavonoids from Tibetan medicine decreases circ_0059665 to alleviate the progression of non-small cell lung cancer under hypoxia.

Gentiana macrophylla Pall. is a traditional Tibetan medicinal herb possessing antinociceptive and anti-inflammatory activities. Circular RNAs (circRNAs) have been identified to be involved in the tumorigenesis of non-small cell lung cancer (NSCLC). Here, this study focused on investigating the function and mechanism of Gentiana macrophylla flavonoids (GF) and circ_0059665 in NSCLC progression. The contents of mRNA and protein were detected using qRT-PCR and western blotting analysis. Cell proliferative and invasive abilities were evaluated by cell counting kit-8, EdU, colony formation and transwell assays, respectively. M2 macrophage polarization was analyzed by flow cytometry. GF treatment suppressed NSCLC cell proliferation, invasion and M2 macrophage polarization under hypoxic conditions. Circ_0059665 was highly expressed in NSCLC tissues and cells. Its expression was increased under hypoxic conditions but was reduced following GF treatment. Furthermore, circ_0059665 overexpression reversed the anticancer effects of GF on NSCLC cells under hypoxic conditions. Mechanistically, circ_0059665 acted as a sponge for miR-512-5p to regulate NOVA2 expression. Hypoxia decreased miR-512-5p levels, and increased NOVA2 levels in NSCLC cells, while these tendencies were abolished after GF treatment. Circ_0059665 silencing inhibited NSCLC cell proliferation, invasion and M2 macrophage polarization in hypoxic environments, which were counteracted by NOVA2 overexpression. Moreover, NOVA2 upregulation reversed the suppressive effects of GF on NSCLC cells with hypoxia treatment. In addition, GF impeded NSCLC tumor growth in vivo via suppressing circ_0059665. GF treatment in hypoxic environments suppressed NSCLC cell proliferation, invasion and M2 macrophage polarization via the circ_0059665/miR-512-5p/NOVA2 axis.

Preventive mechanisms of Chinese Tibetan medicine Triphala against nonalcoholic fatty liver disease

BackgroundTriphala (TLP), as a Chinese Tibetan medicine composing of Emblica officinalis, Terminalia chebula and Terminalia bellirica (1.2:1.5:1), exhibited hepatoprotective, hypolipidemic and gut microbiota modulatory effects. Nonetheless, its roles in prevention of high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) and the related mechanistic insights involving the interplay of gut microbiota and hepatic inflammation are not known. PurposeThe present study seeks to determine if TLP would prevent HFD-induced NAFLD in vivo and its underlying mechanisms from the perspectives of gut microbiota, metabolites, and hepatic inflammation. MethodsTLP was subjected to extraction and chemo-profiling, and in vivo evaluation in HFD-fed rats on hepatic lipid and inflammation, intestinal microbiota, short-chain fatty acids (SCFAs) and permeability, and body weight and fat content profiles. ResultsThe TLP was primarily constituted of gallic acid, corilagin and chebulagic acid. Orally administered HFD-fed rats with TLP were characterized by the growth of Ligilactobacillus and Akkermansia, and SCFAs (acetic/propionic/butyric acid) secretion which led to increased claudin-1 and zonula occludens-1 expression that reduced the mucosal permeability to migration of lipopolysaccharides (LPS) into blood and liver. Coupling with hepatic cholesterol and triglyceride lowering actions, the TLP mitigated both inflammatory (ALT, AST, IL-1β, IL-6 and TNF-α) and pro-inflammatory (TLR4, MYD88 and NF-κB P65) activities of liver, and sequel to histopathological development of NAFLD in a dose-dependent fashion. ConclusionTLP is promisingly an effective therapy to prevent NAFLD through modulating gut microbiota, mucosal permeability and SCFAs secretion with liver fat and inflammatory responses.