The mechanism of Traditional Mongolian medicine Daruqi particles on inflammation.

Daruqi is a Traditional Mongolian medicine with anti-inflammatory, anti-bacterial, and immune-regulatory effects. However, the mechanisms of its activity were unclear. In the present study, we confirmed the anti-inflammation effect of Daruqi on inflammation induced by LPS using animal models. Then, THP-1 cells treated with LPS was used as a positive control to explore the effective component of Daruqi on inflammation. We identified that Oxymatrine was the essential effector of Daruqi. Furthermore, the mechanism of Oxymatrine on inflammation was verified through proteomics analyses and validation assays. Our results demonstrated that Oxymatrine significantly reduced the levels of inflammatory cytokine, including IL-8, IL-1α, and IL-1ß, in LPS induced THP-1 cells. Based on tandem mass tag -labeled quantitative proteomics, 428 differentially expressed proteins were screened, involved in TNF signaling pathway, Ferroptosis, IL-17 signaling pathway, etc. Among these differential expressed proteins (DEPs), 23 proteins were verified with parallel reaction monitoring analysis. The results showed that LPS treatment potentiated the protein level of PLEK, ACSL5 and CYBB, which could be reversed by Oxymatrine. By contrast, the protein expression of SPRYD4 and EMR2 was suppressed after LPS treatment, which could be rescued by Oxymatrine. In summary, Oxymatrine has excellent protective effects in LPS induced THP-1 cells. The five proteins, including PLEK, ACSL5, CYBB, SPRYD4 and EMR2, might serve as the targets of Oxymatrine, and as candidates regulating inflammation in future therapies.

Identification of bioactive ingredients and potential mechanisms of flowers of Hosta Plantaginea in treating pneumonia based on network pharmacology and experimental validation.

Flowers of Hosta plantaginea (H. plantaginea), a widely utilized medicinal herb in Mongolian medicine, holds a significant historical background in terms of its medicinal applications. This herb is renowned for its ability to clear heat and detoxify the body, alleviate cough, and provide relief to the throat. However, the active ingredients and the potential mechanism of action remain ambiguity. The objective of this study was to conduct a comprehensive analysis of the efficacy of H. plantaginea in treating pneumonia, identify its active ingredients and unveil the pharmacological mechanism in the treatment of pneumonia. In vivo experiments demonstrate the plant's anti-pneumonia properties, while mass spectrometry analysis identifies 62 chemicals, with 14 absorbed into the bloodstream. Network pharmacology and Venn analysis reveal 195 targets of 52 active ingredients, with 49 gene targets common to H. plantaginea and pneumonia. Protein-protein interaction (PPI) network construction and enrichment analysis highlight the key targets and pathways such as AKT, EGFR, IL-17. Western blotting confirms downregulation of these pathways, indicating the anti-inflammatory effects of H. plantaginea in treating acute lung injury. Our findings showed that the treatment of ALI with the H. plantaginea exerts its anti-inflammatory effects through multiple components, targets, and pathways. This study established a solid experimental foundation for investigating the various components, targets, and pathways involved in the treatment of pneumonia using H. plantaginea. It offers valuable insights from multiple perspectives and can serve as a reference for the clinical application of this plant in pneumonia treatment.

Exploring the inhibitory impact of Mongolian medicinal He-Zi-3 soup on mammary gland hyperplasia in rats induced by estrogen and progestogen.

ETHNOPHARMACOLOGICAL RELEVANCE: Mammary gland hyperplasia, a prevalent benign breast condition, often serves as a precursor to various other breast diseases. He-Zi-3 soup (HZ-3), a traditional Mongolian remedy, is utilized for treating this condition. AIM OF THE STUDY: To explore the effect and underlying mechanism of HZ-3, a Mongolian medicinal preparation, on mammary gland hyperplasia. MATERIALS AND METHODS: This study aimed to assess the impact of different doses of HZ-3 in a rat model of mammary hyperplasia. The active components within HZ-3 drug serum were identified and analyzed through network pharmacology and target prediction. To elucidate the underlying mechanism of HZ-3 in addressing mammary hyperplasia, we conducted a series of investigations on estradiol-induced mammary hyperplasia in model rates. Assessments included measurements of papilla width and height, hematoxylin and eosin staining, Masson staining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot, and immunohistochemistry. RESULTS: Our investigation revealed the identification of 21 compounds, primarily terpenoids, through serum medicinal chemistry screening. Utilizing network pharmacological analysis, we observed predominant regulation through the estrogen pathway, closely associated with key genes including esr1,esr2, ncoa1, krt 19, ctsd, ebag 9, and bcl-2. Assessments encompassing nipple height and width, histological examination, immunohistochemical analysis, and serum hormone levels via enzyme-linked immunosorbent assay demonstrated the inhibitory effect of HZ-3 on mammary hyperplasia in rat models. RT-qPCR and Western blot analyses corroborated these findings, affirming the suppression of mammary hyperplasia by HZ-3 through the activation of estrogen pathway signaling.

[Mongolian medicine Zhenbao Pill (Eridon Uril) inhibits inflammation and apoptosis in hippocampal neuronal cells of oxyglucose deprived/reoxygenated mice through activation of SIRT1/NF-κB pathway].

Objective To observe the effect of Mongolian medicine Zhenbao Pill (Eridon Uril, EU) on inflammation and apoptosis of HT22 mouse hippocampal neurons cells under oxygen glucose deprivation/reoxygenation (OGD/R), and to explore its potential mechanism. Methods Three-gas incubator and sugar-free anaerobic medium were used to construct a model of OGD/R-injured HT22 cells. OGD/R model cells were treated with EU (10, 20 and 40 µg/mL), and the optimal dose of 20 µg/mL was screened. The OGD/R injured cells treated with nicotinamide (NAM), inhibitor of SIRT1, combined with EU were set as EU combined with NAM group, and the OGD /R injured cells treated with dimethyl sulfoxide (DMSO) combined with EU were set as EU combined with DMSO group. CCK-8 assay and ELISA were used to detect cell activity and LDH leakage rate, respectively. Detection of the mRNA expression of tumor necrosis factor α (TNF-α), Interleukin 6 (IL-6), and IL-1ß was detected by real time fluorescence quantitative PCR in HT22 cells. The apoptosis was detected by flow cytometry. The protein expression of B-cell lymphoma 2 (Bcl2), Bcl2 related X protein (BAX), SIRT1, inhibitor of nuclear factor κB α (IκBα), and phosphorylated nuclear factor κB (p-NF-κB) were detected by Western blot analysis. Results Compared to the control group, HT22 cells in the OGD/R group showed significantly lower activity and higher LDH leakage rate, while (20, 40)µg/mL EU treatment significantly increased cell activity and lowered LDH leakage rate, with 20 µg/mL EU being the optimal dose. The mRNA expression of TNF-α, IL-6 and IL-1ß and the apoptosis rate of the cells in the OGD/R group were significantly higher than those in the control group. The protein levels of SIRT1, IκBα, and Bcl2 were significantly lower than that in the control group, while the protein levels of p-NF-κB, BAX were significantly higher than that in the control group. EU significantly inhibited the secretion of TNF-α, IL-6, IL-1ß and apoptosis in HT22 cells induced by OGD/R. Conclusion EU significantly reduces the inflammatory response and apoptosis in OGD/R-induced mouse hippocampal neurons, which is associated with the activation of SIRT1/NF-κB signal pathway.

Chronic Unpredictable Mild Stress in Rats based on the Mongolian medicine.

Depression is a prevalent affective disorder and constitutes a leading cause of global disability. The limitations of current pharmacological interventions contribute to the substantial health burden attributed to this condition. There is a pressing need for a deeper understanding of the underlying mechanisms of depression, making pre-clinical models with translational potential highly valuable. Mongolian medicine, a subset of traditional medicine, posits that disease occurrence is closely tied to the equilibrium of wind, bile, and Phlegm. In this study, we introduce a protocol for the chronic unpredictable mild stress (CUMS) method in rats. Within this framework, rats are subjected to a series of fluctuating, mild stressors to induce a depression-like phenotype, mimicking the pathogenesis of human depression. Behavioral assays employed in this protocol include the sucrose preference test (SPT), indicative of anhedonia-a core symptom of depression; the open field test (OFT), which measures anxiety levels; and the Morris water maze test (MWM), which evaluates spatial memory and learning abilities. The CUMS method demonstrates the capability to induce anhedonia and to cause long-term behavioral deficits. Furthermore, this protocol is more aligned with Mongolian medical theory than other animal models designed to elicit depression-like behavior. The development of this animal model and subsequent research provide a robust foundation for future innovative studies in the realm of Mongolian medicine.

[Medicinal plant resources in Inner Mongolia autonomous region of China and Mongolia: a comparative study].

Inner Mongolia autonomous region of China and Mongolia are the primary regions where Chinese and Mongolian medicine and its medicinal plant resources are distributed. In this study, 133 families, 586 genera, and 1 497 species of medicinal plants in Inner Mongolia as well as 62 families, 261 genera, and 467 species of medicinal plants in Mongolia were collected through field investigation, specimen collection and identification, and literature research. And the species, geographic distribution, and influencing factors of the above medicinal plants were analyzed. The results revealed that there were more plant species utilized for medicinal reasons in Inner Mongolia than in Mongolia. Hotspots emerged in Hulunbuir, Chifeng, and Tongliao of Inner Mongolia, while there were several hotspots in Eastern province, Sukhbaatar province, Gobi Altai province, Bayankhongor province, Middle Gobi province, Kobdo province, South Gobi province, and Central province of Mongolia. The interplay of elevation and climate made a non-significant overall contribution to the diversity of plant types in Inner Mongolia and Mongolia. The contribution of each factor increased significantly when the vegetation types of Inner Mongolia and Mongolia were broadly divided into forest, grassland and desert. Thus, the distribution of medicinal plant resources and vegetation cover were jointly influenced by a variety of natural factors such as topography, climate and interactions between species, and these factors contributed to and constrained each other. This study provided reference for sustainable development and rational exploitation of medicinal plant resources in future.

Treatment of polycystic ovary syndrome and its associated psychiatric symptoms with the Mongolian medicine Nuangong Qiwei Pill and macelignan.

ETHNOPHARMACOLOGICAL RELEVANCE: The Mongolian medicine Nuangong Qiwei Pill (NGQW) is a folk prescription with a long history of use by the Mongolian people. NGQW comprises seven Mongolian medicines, which have the effects of regulating and nourishing blood, warming the uterus, dispelling cold and relieving pain. For a long time, it has been used as a good remedy for gynecological diseases, with remarkable curative effects, favored by the majority of patients and recommended by doctors. Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder that can lead to menstrual disorders or infertility. In the gynecological classification of Mongolian medicine, polycystic ovary syndrome has not been distinguished in detail, and the mechanism of NGQW in the treatment of polycystic ovary syndrome has not been scientifically studied and standardized. AIM OF THE STUDY: The aim of this study was to clarify the mechanism of action of NGQW and macelignan in the treatment of PCOS and to provide a reference for the clinical application of these drugs. MATERIALS AND METHODS: The effect of intragastric administration of NGQW and macelignan on PCOS model mice was observed. The mental status of mice was examined behaviorally, and serum hormone levels and oxidative stress parameters were measured by ELISA. Giemsa staining was used to detect the reproductive cycle, and HE staining was used to observe the ovarian status. Immunofluorescence staining was performed to observe the proliferation and apoptosis of ovarian granulosa cells. qRT‒PCR was conducted to measure the expression of IL-6, BAX, BCL-2, and estrogen synthesis-related genes in ovarian tissue and particle cells. RESULTS: In the dehydroepiandrosterone (DHEA)-induced PCOS model mice, both NGQW and macelignan improved the estrous cycle; increased the estradiol (E2) content; lowered testosterone (T), progesterone (P) and luteinizing hormone (LH) levels; reduced the number of polycystic follicles; promoted granulosa cell proliferation; reduced granulosa cell apoptosis; and alleviated depression and anxiety. In addition, Nuangong Qiwei Pill and macelignan reduced the mRNA levels of the ovarian inflammatory factor IL-6; improved the disordered levels of the antioxidant indicators GSH, MDA, and SOD; and activated the TGF-ß3 signaling pathway to increase the transcription of Cyp19a1, which increases estrogen secretion. CONCLUSION: NGQW and macelignan can treat PCOS through the TGF-ß3/Smad/Cyp19a1 signaling pathway to regulate the secretion ability of ovarian granulosa cells. Our research justifies the traditional use of NGQW to treat PCOS and enriches the scope of action of macelignan.

Mongolian medicine formulae Ruda-6 alleviates indomethacin-induced gastric ulcer by regulating gut microbiome and serum metabolomics in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ruda-6 (RD-6), a typical traditional Mongolian medicine formulae consisting of 6 herbs, has been traditionally used in treating gastric disorders. Even though it has been shown to protect against gastric ulcers (GU) in animal models, the gut microbiome and serum metabololite-related mechanisms that prevent GU are not well understood. AIM OF THE STUDY: This study was conducted to evaluate the gastroprotective mechanism of RD-6 associated with the alteration of the gut microbiome and serum metabolic profiles in GU rats. MATERIALS AND METHODS: RD-6 (0.27, 1.35 and 2.7 g/kg) or ranitidine (40 mg/kg) were orally administered in rats for three weeks before the induction of gastric ulcer using indomethacin (30 mg/kg, single oral dose). The gastric ulcer index, ulcer area, H&E staining, and the levels of TNF-α, iNOS, MPO and MDA were quantified to evaluate the ulcer inhibitory effects of RD-6. Then, 16S rRNA gene sequencing combined with LC-MS metabolic profiling was performed to investigate the effect of RD-6 on the gut microbiota and serum metabolites in rats. Moreover, a spearman analysis was used to calculate the correlation coefficient between the different microbiota and the metabolites. RESULTS: RD-6 inhibited the gastric lesion damage caused by indomethacin in rats, decreased the ulcer index by 50.29% (p < 0.05), reduced the levels of TNF-α, iNOS, MDA and MPO in gastric tissue. Additionally, RD-6 reshaped the diversity and microbial composition, and reversed the reduced bacteria including [Eubacterium]_xylanophilum group, Sellimonas, Desulfovibrio, and UCG-009, and the increased bacteria Aquamicrobium caused by indomethacin induction. Furthermore, RD-6 regulated the levels of metabolites including amino acids and organic acids, and these affected metabolites were involved in taurine and hypotaurine metabolism and tryptophan metabolism. Spearman analysis revealed that the perturbed gut microbiota were closely related to the changes in differential serum metabolites. CONCLUSION: In view of the 16S rRNA gene sequencing and LC-MS metabolic results, the present study suggests the mechanism of RD-6 ameliorating GU via modulating intestinal microbiota and their metabolites.

Mongolian medicine Wenguanmu ointment treats eczema by inhibiting the CKLF-1/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The main clinical manifestations of eczema include itching, erythema, swelling and pain. Currently, allergies and TH1/TH2 cytokine imbalances are significant causes of eczema. TCM believes that eczema is mainly caused by incongruity between dry and wet. Wenguanmu ointment is a classic Mongolian medicine, which mainly composed of Xanthoceras sorbifolia Bunge, Coptis chinensis Franch and Bezoar. These ingredients can clear heat and dampness, dispel wind and dehumidification, anti-inflammatoryad analgesic. In this study, it was found that Wenguanmu ointment can treat eczema with anti-inflammatory, analgesic and antipruritic. AIM OF THE STUDY: In this study, the content of main components in Wenguanmu ointment was tested. Moreover, the therapeutic effect and mechanism of Wenguanmu ointment on eczema model mice were studied. MATERIALS AND METHODS: Kunming mice (25 ± 2 g) were randomly divided into 6 groups: Control group; Model group; Vehicle group; Wenguanmu ointment group; Compound dexamethasone acetate cream group; Chushizhiyang ointment group. The eczema mouse model was established by DNCB. HPLC and TLC tests were used to determine the content of the main components in Wenguanmu ointment. HE staining was used to assess skin damage in mice. In order to detect the anti-inflammatory effect of Wenguanmu ointment on eczema, The levels of IgE, TNF-α, IFN-γ, COX-2 and IL-4 in serum was measured by ELISA. Genecards and Online Mendelian Inheritance in Man databases were used to analyze potential target gene predictions, and it was speculated that Wenguanmu ointment was associated with NF-κB signaling pathway and chemokine signaling pathway. To detect this inference, RT-qPCR and western blotting were used to detect protein and mRNA levels of CKLF-1, IκB-α, and NF-κB. RESULTS: Wenguanmu ointment can repress the symptoms of eczema caused by 2, 4-dinitrochlorobenzene, and inhibit the level of serum immunoglobulin E. Simultaneously it restrain the elevation of miscellaneous pro-inflammatory cytokines and chemokines, as well as reducing the expression of CKLF-1 and NF-κB protein in the nucleus, and increasing the protein expression of IκB to improve eczema. CONCLUSIONS: The ameliorating effect of Wenguanmu ointment on eczema lesions can play a importment role by inhibiting the CKLF-1/NF-κB pathway.

Mechanism of the Mongolian medicine Eerdun Wurile basic formula in improving postoperative cognitive dysfunction by inhibiting apoptosis through the SIRT1/p53 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Mongolian medicine Eerdun Wurile is a commonly used Mongolian in folk medicine used to treat cerebral nervous system diseases such as cerebral hemorrhage, cerebral thrombosis, nerve injury and cognitive function, cardiovascular diseases such as hypertension and coronary heart disease. Eerdun wurile may effect anti-postoperative cognitive function. AIM OF THE STUDY: To investigate the molecular mechanism of the Mongolian medicine Eerdun Wurile Basic Formula (EWB) in improving postoperative cognitive dysfunction (POCD) based on Network pharmacology, and to confirm involvement of the SIRT1/p53 signal pathway, one of the key signal pathways, by using the POCD mouse model. MATERIAL AND METHODS: Obtain compounds and disease-related targets through TCMSP, TCMID, PubChem, PharmMapper platforms, GeneCards, and OMIM databases, and screen intersection genes; Use Cytoscape software to build a "drug-ingredient-disease-target" network, and the STRING platform for protein interaction analysis.; R software was used to analyze the function of gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment.; AutoDock Vina software for active components and core targets to Perform molecular docking. The POCD mouse model was prepared by intracerebroventricular injection of lipopolysaccharide (LPS), and the morphological changes of hippocampal tissue were observed by hematoxylin-eosin (HE) staining, Western blot, immunofluorescence and TUNEL were used to verify the results of network pharmacological enrichment analysis. RESULTS: There were 110 potential targets for improving POCD by EWB, 117 items were enriched by GO, and 113 pathways were enriched by KEGG, among which the SIRT1/p53 signaling pathway was related to the occurrence of POCD. Quercetin, kaempferol, vestitol, ß-sitosterol and 7-methoxy-2-methyl isoflavone in EWB can form stable conformations with low binding energy with core target proteins IL-6, CASP3, VEGFA, EGFR and ESR1. Animal experiments showed that compared with the POCD model group, the EWB group could significantly improve the apoptosis in the hippocampus of the mice, and significantly down-regulate the expression of Acetyl-p53 protein (P < 0.05). CONCLUSION: EWB can improve POCD with the characteristics of multi-component, multi-target, and multi-pathway synergistic effects. Studies have confirmed that EWB can improve the occurrence of POCD by regulating the expression of genes related to the SIRT1/p53 signal pathway, which provides a new target and basis for the treatment of POCD.

[Mongolian medicine Heisuga-25 promotes the expression of neuroskeletal protein, increases the content of neurotransmitter and improves the symptoms of Alzheimer's disease in mice].

Objective To investigate the effect and mechanism of Mongolian medicine Heisuga-25 on Alzheimer's disease (AD) mice. Methods Six month old SAMP8 mice were divided into model group, Heisuga-25 [360 mg/(kg.d), 90 mg/(kg.d)] treatment group, and donepezil control group[0.92 mg/(kg.d)], with 15 mice in each group. Another 15 6-month-old normal aging SAMR1 mice were selected as blank control group. The mice in the model group and blank control group were fed with normal saline, and the other groups were gavaged according to the dosage. All groups were gavaged once a day for 15 days. From Day 1 to Day 5 after administration, three mice in each group were taken and Morris water maze test was been used to detect the escape latency, times for crossing the platform and the residence time were detected. Nissl staining was used to observe the number of Nissl bodies. Western blot analysis and immunohistochemistry were used to detect the expression of microtubule associated protein 2 (MAP-2) and low molecular weight neurofilament protein (NF-L). ELISA was used to detect the contents of acetylcholine (ACh), 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA) in cortex and hippocampus of mice. Results Compared with the blank control group, the escape latency was significantly prolonged, while the model group showed a decrease in the number of crossing the platform, residence time, Nissl bodies, and the protein expression of MAP-2 and NF-L. Compared with the model group, Heisuga-25 administration group exhibited an increase in the number of crossing the platform and residence time, Nissl bodies, and the protein expression of MAP-2 and NF-L, but a shortened escape latency. The effect of high-dose groupHeisuga-25 [360 mg /(kg.d)] on the above indexes was more obvious. Compared with the blank control group, the contents of ACh, NE, DA and 5-HT in hippocampus and cortex were decreased in the model group. Compared with the model group, the low-dose group, high-dose group and donepezil control group all observed an increase in the contents of ACh, NE, DA and 5-HT. Conclusion Mongolian medicine Heisuga-25 can improve learning and memory by protecting the neural function of AD model mice, which may be accounted for up-regulation of neuronal skeleton protein expression and increased content of neurotransmitters.

Behavioral and Network Pharmacology-Based Analyses for the Traditional Mongolian Medicine Zadi-5 in a Rat Model of Depression.

Zadi-5 is a traditional Mongolian medicine that is widely used for the treatment of depression and symptoms of irritation. Although the therapeutic effects of Zadi-5 against depression have been indicated in previously reported clinical studies, the identity and impact of the active pharmaceutical compounds present in the drug have not been fully elucidated. This study used network pharmacology to predict the drug composition and identify the therapeutically active compounds in Zadi-5 pills. Here, we established a rat model of chronic unpredicted mild stress (CUMS) and conducted an open field test (OFT), Morris water maze (MWM) analysis, and sucrose consumption test (SCT) to investigate the potential therapeutic efficacy of Zadi-5 in depression. This study aimed to demonstrate Zadi-5's therapeutic effects for depression and predict the critical pathway of the action of Zadi-5 against the disorder. The vertical and horizontal scores (OFT), SCT, and zone crossing numbers of the fluoxetine (positive control) and Zadi-5 groups were significantly higher (P < 0.05) than those of the CUMS group rats without treatment. According to the results of network pharmacology analysis, the PI3K-AKT pathway was found to be essential for the antidepressant effect of Zadi-5.

Amelioration of chronic prostatitis by fractions of Mongolian medicine Hosta plantaginea flowers via inhibition of NF-κB, MAPKs, JAK-STAT, and PI3K-Akt signaling pathways in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Hosta plantaginea (Lam.) Aschers flower is an important Mongolian medicine beneficial in the treatment of chronic prostatitis (CP) in the absence of scientific evidence. AIM OF THE STUDY: The aim of this study was to reveal the therapeutical effects and potential mechanisms of H. plantaginea flowers extract (HP) and its different polarity fractions (HPA∼D) on autoimmune CP (ACP) model rats. MATERIALS AND METHODS: Sprague-Dawley male rats were randomly assigned to 13 groups (n = 6/group). Except the sham group, all rats were injected with a mixture of prostate antigen and complete Freund's adjuvant on days 0, 7, and 21 to establish ACP model rats. Afterwards, ACP model rats were orally gavaged with HP or HPA∼D (1 and 4 g/kg of raw herbal material) or positive drug (Prostat, 200 mg/kg) daily from day 21 to day 50 for 30 days, while the sham and model groups were treated simultaneously with isopyknic of 0.3% sodium carboxymethyl cellulose. Histopathological analysis, biochemical parameters, and protein expression of prostate tissues were investigated. RESULTS: In comparison with the model group, all fraction groups experienced improved CP effects, including restored body weight, reduced prostate gland edema and prostate index, decreased prostatic leukocytes, increased prostatic lecithin bodies, and alleviated histopathological damage to prostate tissue. Furthermore, all fraction groups markedly inhibited the phosphorylated protein of nuclear factor kappa-B p65 (NF-κB p65), NF-κB inhibitor alpha (IκBα), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (Erk), just another kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) than the model group. CONCLUSION: All fractions of HP exerted significant anti-CP effects by inhibiting NF-κB, MAPKs, JAK-STAT and PI3K-Akt pathways in ACP model rats. These findings provide scientific evidence that H. plantaginea flowers can be used as a pivotal Mongolian medicine in clinical applications for the treatment of CP.

Exploring the Active Compounds of Traditional Mongolian Medicine Baolier Capsule (BLEC) in Patients with Coronary Artery Disease (CAD) Based on Network Pharmacology Analysis, Molecular Docking and Experimental Validation.

Objective: Baolier Capsule (BLEC) is a Traditional Mongolian Medicine comprising fifteen herbs. This study aims to illustrate the synergistic mechanism of BLEC in the treatment of Coronary Artery Disease (CAD) by using network pharmacology method, molecular docking and experimental validation. Methods: Searching and screening the active ingredients of different herbs in BLEC and target genes related to CAD in multiple databases. Subsequently, Protein-Protein Interactions Network (PPI-Net), gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment were used to identify the key targets. AutoDock was used to verify the binding ability between the active ingredient and key target through molecular docking. Reverse Transcription-Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR) was used to verify the effect of active ingredient of BLEC on the key target gene. Finally, effect of BLEC on the degree of blood lipids and atherosclerosis was validated by animal experiment. Results: There are 144 active components and 80 CAD-related targets that are identified in BLEC in the treatment of CAD. What is more, 8 core genes were obtained by clustering and topological analysis of PPI-Net. Further, GO and KEGG analysis showed that fluid shear stress and atherosclerosis are the key pathways for BLEC to treat CAD. These results were validated by molecular docking method. In vitro, active compounds of BLEC (Quercetin, luteolin, kaempferol, naringenin, tanshinone IIA, ß-carotene, 7-O-methylisomucronulatol, piperine, isorhamnetin and Xyloidone) can inhibit 8 core gene (AKT1, EGFR, FOS, MAPK1, MAPK14, STAT3, TP53 and VEGFA) expression. Moreover, BLEC not only improve blood lipid levels but also inhibit the development of atherosclerosis in ApoE-knockout mice. Conclusion: Our research first revealed the basic pharmacological effects and related mechanisms of in the treatment of CAD. The predicted results provide some theoretical support for BLEC or its important active ingredients to treat CAD.

The Ethanol Extract of Syringa oblata Heartwood, a Mongolian Folk Medicine Containing Major Lignans, Exerts Analgesic and Sedative Effects on Mice.

The heartwood of Syringa oblata Lindl. (SO) is one of Mongolian folk medicines to treat insomnia and pain, while its pharmacological evaluation and underlying mechanism remain unclear. In this study, the sedative effect of ethanol extract of SO (ESO) was evaluated with the locomotor activity test and the threshold dose of pentobarbital sodium-induced sleep test in mice, and the hot plate test, acetic acid-induced writhing test, and formalin test in mice were used to evaluate its analgesic effect. The underlying mechanism of ESO analgesia was explored by RT-PCR and western blot analysis, which is associated with the regulation of the NF-κB signaling pathway. Besides, the main constituents of ESO were characterized by LC/MS data analysis and comparison with isolated pure compounds. The current findings brought evidence for clinical application and further pharmacological and phytochemical studies on SO.

Secondary metabolites from the Mongolian medicine Lomatogonium carinthiacum.

Systematic phytochemical investigation on the Mongolian medicinal herb Lomatogonium carinthiacum led to the isolation of 12 monoterpenoids including three new secoiridoids (1, 2 and 4) and one new iridoid glycoside (13), one new monoterpenoid alkaloid (3), and three new sesquiterpenoids (14-16). Comprehensive spectroscopic analysis (including 1D and 2D NMR, and HRESIMS) and quantum chemistry computations (including ECD and NMR calculations) were applied to elucidate their structures. Weak immunosuppressive activities were observed for the new isolates via inhibiting T cell proliferation and cytokine IFN-γ secretion in vitro.

RNA-Seq Reveals Protective Mechanisms of Mongolian Medicine Molor-Dabos-4 on Acute Indomethacin-Induced Gastric Ulcers in Rats.

This study aimed to apply transcriptomics to determine how Molor-Dabos-4 (MD-4) protects healthy rats against indomethacin (IND)-induced gastric ulcers and to identify the mechanism behind this protective effect. Rats were pretreated with MD-4 (0.3, 1.5, or 3 g/kg per day) for 21 days before inducing gastric ulcers by oral administration with indomethacin (30 mg/kg). Unulcerated and untreated healthy rats were used as controls. Effects of the treatment were assessed based on the ulcer index, histological and pathological examinations, and indicators of inflammation, which were determined by enzyme-linked immunosorbent assay. Transcriptomic analysis was performed for identifying potential pharmacological mechanisms. Eventually, after identifying potential target genes, the latter were validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). After pretreatment with MD-4, gastric ulcers, along with other histopathological features, were reduced. MD-4 significantly (p < 0.05) increased the superoxide dismutase (SOD) levels in ulcers and reduced pepsin, TNF-α, and IL-6 levels. RNA-seq analysis identified a number of target genes on which MD-4 could potentially act. Many of these genes were involved in pathways that were linked to anti-inflammatory and antioxidant responses, and other protective mechanisms for the gastric mucosa. qRT-PCR showed that altered expression of the selected genes, such as Srm, Ryr-1, Eno3, Prkag3, and Eef1a2, was consistent with the transcriptome results. MD-4 exerts protective effects against IND-induced gastric ulcers by reducing inflammatory cytokines and pepsin and increasing the expression of SOD levels. Downregulation of Srm, Ryr-1, Eno3, Prkag3, and Eef1a2 genes involved in regulating arginine and proline metabolism, calcium signaling pathway, HIF-1 signaling pathway, oxytocin signaling pathway, and legionellosis are possibly involved in MD-4-mediated protection against gastric ulcers.

Gurgem-7 toxicity assessment: Regulation of cell survival or death by traditional Mongolian prescription.

Surgical treatments and chemotherapy are the most commonly used methods of colorectal cancer treatment (CRC), unfortunately, these therapies have many side effects. Moreover, despite advances in primary and adjuvant treatments, the survival time in CRC patients is still unsatisfactory. Treatment options for patients with CRC continue to advance and recent research has shown that colorectal cancer is sensitive to plant-derived substances. The use of natural compounds contained in herbal extracts for the treatment of colon cancer or as adjunctive therapy for CRC gives patients a wide range of treatment options. In this study, we evaluate the potential toxicity of the Mongolian preparation - Gurgem-7 composed of Crocus sativus, Veronica officinalis, Capsella bursa-pastoris, Arctostaphylos uva-ursi, Calendula officinalis, Gentiana lutea, and Terminalia chebula. Therefore, the aim of this study was to determine its biological activities, biochemical and molecular features in vitro and composition analysis by HPLC-ESI-QTOF-MS/MS platform. We identified 18 metabolites and 8 of them were quantified. Majority of the secondary metabolites belonged to the group of phenolic constituents with taxifolin, chlorogenic acids' family, hydroxysafflor yellow A and hydroxybenzoic acid as leading compounds. In turn, our in vitro results suggest that the preparation inhibits cell metabolic activity through oxidative stress, numerous DNA damage and cell cycle arrest. Simultaneously enzymatic and non-enzymatic cell protection mechanisms mediated by TP53/Keap1 and Nrf2/HO-1 pathways may be activated in a cell-specific manner in vitro. In conclusion, we provide preliminary molecular evidence of the toxic properties of Gurgem-7 preparation to Caco-2 and CT26. WT cells related to insufficient action of their repair and adaptive mechanisms to stress conditions.

Mongolian Medicine Areca Thirteen Pill (GY-13) Improved Depressive Syndrome via upregulating cAMP/PKA/CREB/BDNF signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Areca Thirteen Pill, also called Gao You-13 (GY-13), is a traditional Mongolian herbal formula and has been extensively used to treat depression in Mongolian areas, which belongs to Heyi disease in Mongolian medicine. Major depressive disorder is a serious psychiatric disease, only one-third of individuals with depression are responsive to current antidepressants in clinic. Growing attention has been attracted by traditional herbal medicines in fighting depression because they are considered safer alternatives to pharmacotherapy. AIM OF THE STUDY: To reveal the mechanism of GY-13 in the treatment of depression. MATERIALS AND METHODS: The rat depression model was established by chronic unpredictable mild stress (CUMS), and primary hippocampal neurons were used to construct a glutamate-induced excitotoxicity model. The antidepressant effect of GY-13 was then assessed by performing sucrose preference tests, open field tests, and body weight measurements on rats. The expression of cAMP and PKA, mRNA levels of brain-derived neurotrophic factor (BDNF) and cAMP response element binding protein (CREB), and hippocampal neuronal apoptosis were measured. RESULTS: The results indicate that GY-13 significantly improves depression-like behavior, rescues decreased cAMP， PKA, recovers the mRNA levels of CREB and BDNF, and increases the proliferative activity of hippocampus. In addition, blockade of PKA reverses the effects of GY-13 treatment on CREB mRNA, BDNF mRNA levels. In vitro, GY-13 treatment increased hippocampal proliferative activity and attenuated Glu-induced apoptosis of hippocampal neurons as well as reduced CREB mRNA and BDNF mRNA expression levels. CONCLUSIONS: Our research demonstrated that GY-13 treatment exerted a potent antidepressant action via activation of cAMP/CREB/BDNF signaling pathway, promoting proliferation, and suppressing apoptosis. This research provides molecular biological ground for developing GY-13 into a potent alternative for the intervention of depression.