[Research progress on bioactive constituents and pharmacological effects of Tibetan medicine Sinopodophylli Fructus].

Sinopodophylli Fructus is a traditional medicine used by the Tibetan people. It is known for its ability to regulate menstruation and promote blood circulation. Presently, bioactive constituents that have been isolated and identified from Sinopodophylli Fructus mainly include 15 lignans(e.g., podophyllotoxin, deoxypodophyllotoxin, and 4'-demethylpodophyllotoxin) and 20 flavonoids(e.g., quercetin, kaempferol, and rutin). These components exhibit pharmacological effects such as anticancer, antibacterial, and lipid-lowering activities. Additionally, Sinopodophylli Fructus contains other components such as proteins, fatty acids, polysaccharides, vitamins, amino acids, and trace elements. According to the relevant literature reports in China and abroad, this article reviewed the chemical constituents and pharmacological effects of Sinopodophylli Fructus, aiming to provide references for the development and rational clinical application of this medicinal resource.

Areca Thirteen Pill Improves Depression in Rat by Modulation of the Chemokine/Chemokine Receptor Axis.

Depressive disorder is a severe and complex mental illness. There are a few anti-depressive medications that can reduce depressive symptoms, but with adverse or side effects. GaoYou-13 (GY-13), commonly known as Areca Thirteen Pill, is a traditional medicine for depression treatment with significant clinical impact. However, the molecular mechanism of GY-13 has not been fully elucidated. This study aimed to explore and explain the action and mechanism of GY-13 in treatment for depression. SD male rats were stimulated differently daily for 42 days to construct a depression rat model and divided into six groups: the control, CUMS model, GY-13L, GY-13 M, GY-13H, and FLUO. The body weight of was measured on day 7, 14, 21, 28, 35, and 42 or different days, and the behavioral tests (Open-field test, Sucrose preference test, Morris water maze) were made alongside. After the rats were decapitated, the rat brains were stained with Nissl or H&E dyes. The serums of TNF-α and IL-1ß were tested. The protein of p-IKKα, p-IкBα, and p-NFкBp65 was traced. Then nano-LC-MS/MS analysis was made to detect the mechanism of GY-13. The active ingredients, drug targets, and key pathways of GY-13 in treating depression were analyzed through network pharmacology and molecular docking. With immunohistochemistry, quantitative RT-PCR, and western-blot techniques, the therapeutic mechanism of GY-13 was traced and analyzed. This study revealed that GY-13 significantly enhances autonomous and exploratory behavior, sucrose consumption, learning and memory ability, and hippocampal neuronal degeneration, which inhibits inflammation. In addition, omics analysis showed several proteins were altered in the hippocampus of rats following CUMS and GY-13 treatment. Bioinformatics analysis and network pharmacology revealed the antidepressant effects of GY-13 are related to the chemokine/chemokine receptor axis. Immunohistochemistry, western blotting and RT-PCR assay further support the findings of omics analysis. We highlighted the importance of the chemokine/chemokine receptor axis in the treatment of depression, as well as showed GY-13 can be used as a novel targeted therapy for depression treatment.

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.

Anshen Buxin Liuwei Pill, a Mongolian Medicinal Formula, Could Protect H2O2-Induced H9c2 Myocardial Cell Injury by Suppressing Apoptosis, Calcium Channel Activation, and Oxidative Stress.

BACKGROUND: Anshen Buxin Liuwei pill (ABLP) is a Mongolian medicinal formula which has a therapeutic effect on the symptoms such as coronary heart disease, angina pectoris, arrhythmia, depression and irritability, palpitation, and short breath. However, its bioactivity against cardiac injury remains unclear. METHODS: The protective effect of ABLP was evaluated using H9c2 cells. Cell viability, intracellular Ca2+, reactive oxidative indices, and mitochondrial membrane potential (∆ψ) were assessed, respectively. The mRNA levels of Ca2+ channel-related genes (DHPR, RyR2, and SCN5A) and oxidative stress-related genes (Keap1, Nrf2, and HO-1) were measured by RT-PCR. RESULTS: 0.5-50 µg/mL ABLP could significantly decrease H2O2-induced cell injury by suppressing cell necrosis/apoptosis and excess oxidative stress, ameliorating the collapse of ∆ψ, and reducing intracellular Ca2+ concentration. Furthermore, 0.5-50 µg/mL ABLP reversed H2O2-induced imbalance in the mRNA levels of DHPR, RyR2, SCN5A, Keap1, Nrf2, and HO-1 gene in H9c2 cells, which further illustrate the mechanism. CONCLUSION: ABLP provided protective and therapeutic benefits against H2O2-induced H9c2 cell injury, indicating that this formula can effectively treat coronary disease. In addition, the present study also provides an in-depth understanding of the pharmacological functions of ABLP, which may lead to further successful applications of Mongolian medicine.

Anshen-Buxin-Liuwei pill, a Mongolian medicinal formula could alleviate cardiomyocyte hypoxia/reoxygenation injury via mitochondrion pathway.

BACKGROUND: Anshen Buxin Liuwei pill (ABLP) is a Mongolian medicinal formula that is composed of six medicinal materials: the Mongolian medicine Bos taurus domesticus Gmelin, Choerospondias axillaris (Roxb.) Burtt et Hill, Myristica fragrans Houtt., Eugenia caryophµllata Thunb., Aucklandia lappa Decne., and Liqui dambar formosana Hance. ABLP is considered to have a therapeutic effect on symptoms such as coronary heart disease, angina pectoris, arrhythmia, depression and irritability, palpitation, and shortness of breath. METHODS: H9c2 cardiomyocytes were used to construct a hypoxia/reoxygenation (HR) injury model. CCK-8 assay and Annexin V-FITC cell apoptosis assays were used for cell viability and cell apoptosis determination. The LDH, SOD, MDA, CAT, CK, GSH-Px, Na+-K+-ATPase, and Ca2+-ATPase activities in cells were determined to assess the protective effects of ABLP. The mRNA levels of Sirtuin3 (Sirt3) and Cytochrome C (Cytc) in H9c2 cells were determined by quantitative real-time PCR. RESULTS: The results indicate that HR-treated cells began to shrink from the spindle in an irregular shape with some floated in the medium. By increasing the therapeutic dose of ABLP (5, 25, and 50 µg/mL), the cells gradually reconverted in a concentration-dependent manner. The release of CK in HR-treated cells was significantly increased, indicating that ABLP exerts a protective effect in H9c2 cells against HR injury and can improve mitochondrial energy metabolism and mitochondrial function integrity. The present study scrutinized the cardioprotective effects of ABLP against HR-induced H9c2 cell injury through antioxidant and mitochondrial pathways. CONCLUSIONS: ABLP could be a promising therapeutic drug for the treatment of myocardial ischemic cardiovascular disease. The results will provide reasonable information for the clinical use of ABLP.

The complete chloroplast genome of Stemona tuberosa Lour (Stemonaceae).

Stemona tuberosa Lour is a perennial herb in the family of Stemonaceae. It is commonly used as traditional medicine in China. Here, we assembled and annotated the complete chloroplast genome of S. tuberosa. The chloroplast genome was 154,374 bp in length, containing a typical quadripartite structure with a large single copy (LSC) of 82,305 bp, a small single copy (SSC) of 17,929 bp, and two inverted repeats (IRa and IRb) regions of 27,070 bp each. The overall GC content of the genome was 37.88%. A total of 134 genes were annotated in the chloroplast genome, including 88 protein-coding genes, 38 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. Phylogenetic analysis suggested that S. tuberosa was closely related to S. japonica and S. mairei.

The complete chloroplast genome of Polygonatum cirrhifolium (Wall.) Royle, a medicine herb.

Polygonatum cirrhifolium (Wall.) Royle is a medicinal plant of commercial value. In the present study, we assembled the complete chloroplast genome of P. cirrhifolium. The total genome was a circular DNA molecule of 155,583 bp, which was made up of a large single copy region (84,412 bp), a small single copy region (18,427 bp), and a pair of inverted repeat regions (26,372 bp each). A total of 133 genes was annotated in the chloroplast genome, including 85 protein-coding genes, 40 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. Overall, the chloroplast genome had a GC content of 37.66%. Phylogenetic analysis showed that P. cirrhifolium was closely related to P. kingianum.

Systems pharmacology-based dissection of mechanisms of Tibetan medicinal compound Ruteng as an effective treatment for collagen-induced arthritis rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Ruteng (CRT) is a prescribed formulation based on the theory of Tibetan medicine for the treatment of yellow-water-disease. It is consisted with 7 medicinal material include Boswellia carterii Birdw (named "Ruxiang" in Chinese); Tinospora sinensis (Lour.) Merr. (named "Kuan-Jin-Teng" in Chinese), Cassia obtusifolia L (named "Jue-Ming-Zi" in Chinese); Abelmoschus manihot (L.) Medic (named "Huang-Kui-Zi" in Chinese); Terminalia chebula Retz. (named "He-Zi" in Chinese); Lamiophlomis rotata (Benth.) Kudo (named "Du-Yi-Wei" in Chinese) and Pyrethrum tatsienense (Bur. et Franch.) Ling (named "Da-Jian-Ju" in Chinese). They are widely distributed in Tibet area of China and have been used to treat rheumatism, jaundice, and skin diseases for centuries. AIM OF THE STUDY: The present study was conducted to investigate the anti-arthritis effect of CRT and to disclose the systems pharmacology-based dissection of mechanisms. MATERIALS AND METHODS: The chemical constituents in CRT were identified using HPLC method, and CRT candidate targets against RA were screened by network pharmacology-based analysis and further experimentally validated based on collagen-induced arthritis (CIA) rat model. Furthermore, therapeutic mechanisms and pathways of CRT were investigated. RESULTS: 391 potential targets (protein) were predicted against 92 active ingredients of 7 medicinal materials in CRT. Enrichment analysis and molecular docking studies also enforced the practiced results. X-ray based physiological imaging showed the attenuated effect of CRT on paw swelling, synovial joints and cartilage with improved inflammation in CIA rats. Moreover, the expression of biomarkers associated with RA such as MMP1, MMP3 and MMP13 and TNF-a, COX2 and iNOS are down-regulated in ankle joints, serum, or liver. CONCLUSION: In conclusion, CRT compound could attenuate RA symptoms and active ingredients of this compound could be considered for drug designing to treat RA.

Sweroside Alleviated Aconitine-Induced Cardiac Toxicity in H9c2 Cardiomyoblast Cell Line.

Aconitine is the main bioactive ingredient of Aconitum plants, which are well-known botanical herbs in China. Aconitine is also notorious for its high cardiotoxicity, as it can induce life-threatening ventricular arrhythmias. Unfortunately, there are few effective antidotes to aconitine toxicity. This study aimed to evaluate the potent protective effects of the ingredients from V. baillonii on aconitine toxicity on H9c2 cell line. Cell viability was assessed by methylthiazoltetrazolium bromide (MTT). Intracellular Ca2+ concentration alteration and reactive oxygen species (ROS) generation were observed by confocal microscopy and flow cytometry, respectively. Cellular oxidative stress was analyzed by measuring malondialdehyde (MDA) and superoxide dismutase (SOD) levels. Mitochondrial membrane potential (ΔΨ) was determined using JC-1 kit. RT-PCR and Hoechst staining techniques were conducted to determine the levels of autophagy/apoptosis. The mRNA levels of dihydropyridine receptor (DHPR), ryanodine receptors (RyR2) and sarcoplasmic reticulum Ca2+-ATPase (SERCA) were measured by RT-PCR. We screened six components from V. baillonii, among which, sweroside exhibited the strongest protective effects on aconitine-induced cardiac toxicity. Sweroside suppressed the aconitine-induced mRNA expressions of NaV1.5 (encoded by SCN5A), RyR2 and DHPR, and reversed the aconitine-induced decrease in mRNA level of SERCA, thus preventing the aconitine-induced persistent intracellular Ca2+ accumulation and avoiding intracellular Ca2+ overload. We further found that sweroside restabilized the aconitine-disrupted mitochondrial membrane potential (ΔΨ) and reversed the aconitine-induced increase in the mRNA levels of cell autophagy-related factors (Beclin-1, Caspase-3, and LC3- II) in H9c2 cells. In the whole-animal experiments, we observed that sweroside (50 mg/kg) alleviated effectively aconitine-induced arrhythmias by analysis of electrocardiogram (ECG) recording in rats. Our results demonstrate that sweroside may protect cardiomyocytes from aconitine toxicity by maintaining intracellular Ca2+ homeostasis, restabilizing mitochondrial membrane potential (ΔΨ) and avoiding cell autophagy/apoptosis.

[Referencing and inosculating--discussion on modern research strategy for ethnomedicines].

This article reviewed the current situation of ethnomedicines in China, and propos that the important research on ethnomedicine is to focus on the theoretical and empirical characteristics of ethnomedicine and the special features in the processes of collecting,processing and clinical application of ethnomedicine, which will be benefit to find the research principles and methods with the characteristics of ethnomedicine. These principles include making clear of the effective substances and mechanisms, and theoretical and empirical characteristics of ethnomedicine. The three methods in the new drug discovery technology system for ethnomedicine are to solve the difference in varieties of traditional medical systems depending on finding the similarities of them, to find the conjunction in varieties of traditional medical systems through the key-herbs, and to find medicinal sources in varieties of traditional medical systems according to pharmaphylogeny.

[Effects of Betel shisanwei ingredients pill on AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depressive rats].

OBJECTIVE: To observe the effects of Mongolian pharmaceutical Betel shisanwei ingredients pill on AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depressive rats. METHOD: Sixty male Wistar rats were randomly divided into six groups according to the sugar consumption test (10 rats in each group), normal control group,model group,fluoxetine group (3.3 mg x kg(-1)) and low dose, medium dose and high dose group (0.25, 0.5, 1 g x kg(-1)) of Betel shisanwei ingredients pill. Except the normal control,the other groups were treated with the chronic unpredictable mild stress stimulation combined with lonely raising for 28 days. 10 mL x kg(-1) of drugs were given to each rat once daily,continuously for 28 days. The AC activity of the hippocampus and prefrontal cortex were determined by radiation immunity analysis (RIA), while cAMP and PKA quantity were determinated by Enzyme-linked immunosorbent (ELISA). RESULT: The AC activity, cAMP and PKA quantity of hippocampus and prefrontal of mouse model of Chronic stress depression decreased significantly than those of control group (P < 0.05 or P < 0.01). However, the AC activity, cAMP and PKA quantity of rat hippocampus and prefrontal cortex in the fluoxetine group and the Mongolian pharmaceutical Betel shisanwei ingredients pill group indecreased significantly than those of model group (P < 0.01 or P < 0.05). Especially for the high dose group of Mongolian pharmaceutical Betel shisanwei ingredients pill. CONCLUSION: The AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depression model of rats is down-regulated, whereas Mongolian pharmaceutical Betel shisanwei ingredients pill could up-regulated it to resist depression.

[Research of steroidal saponins from the fresh rhizomes of Dioscorea zingiberensis].

OBJECTIVE: To study the steroidal saponins from the fresh rhizomes of Dioscorea zingiberensis and search for new bioactive compounds. METHODS: The steroidal saponins were isolated by normal phase silica gel and RP-C18 column chromatography, their chemical structures were elucidated by MS and NMR methods. RESULTS: One steroidal saponin was isolated from EtOH extract of the fresh rhizomes of D. zingiberensis and identified as 26-O-beta-D-glucopyranosyl-3beta, 22alpha, 26-trihydroxy-25(R)-furosta-5-en-3-O-[alpha-L-rhamnopyranosyl-(1 --> 4) ]-beta-D-glucopyranoside. CONCLUSION: This compound is isolated from Dioscorea L. the first time.

[Effect of Chinese herb medicine compound on bone loss in rats under 3 weeks simulated weightlessness: preliminary study].

OBJECTIVE: To investigate the effect of Chinese herb medicine compound on bone lose in rats under 3 weeks simulated weightlessness, and to observe the synergistic action of other ingredients in the compound on calcium. METHODS: Thirty male Wistar rats were divided into 3 groups: control group, tail-suspend group, tail-suspend and medicine group which took Chinese herb medicine compound (contains Radix Rehmanniae Praeparata, Radix Achyranthis Bidentatae, Radix Astragali, Radix Angelicae Sinensis, Concha Ostreae prepared by acetic acid) by gastric administration. After 3 weeks simulated weightlessness, serum calcium (Ca), phosphorus (P), bone mineral density (BMD) and content (BMC), bone mechanical properties (MEC) were observed. RESULTS: At the end of the experiment, serum Ca and P increased significantly (P<0.01), BMD and BMC of posterior body decreased significantly (P< 0.01) in tail suspend rats, compared with in the control group. In rats of tail suspended and medicine group, the increase degree of serum Ca and P were smaller, BMD and BMC of posterior body increased significantly (P<0.01 or 0.05), and MEC also tend to increase. CONCLUSION: Bone mass of posterior body lose significantly, with mechanical property significantly decrease in rats after 3 weeks simulated weightlessness. Chinese herb medicine compound is effective to prevent the change of bone. Simple calcium supplement can not prevent simulated weightlessness induced bone loss, therefore other ingredients in the compound may perform synergistic action to calcium (Concha Ostreae prepared by acetic acid).

[Effects on rats' bone mineral density and bone biomechanics by suspensory simulated weightlessness and removing suspension].

OBJECTIVE: To study the effects on rats' bone mineral density and bone biomechanics by suspensory simulated weightlessness and removing suspension. METHODS: Twenty Wistar rats were divided into two groups randomly as control group and model group. Suspend the model group rats for 14 days, then remove suspension and continue to feed for another 14 days. Feed control group rats for 28 days. Detect the bone mineral density (BMD) in vivo of cranial bone, second thoracic vertebra, fourth lumbar vertebra, pelvis, right radioulna and right femoral bone of each group at the 14th day. At the 28th day,execute all the rats and take out of right femoral bone and fourth lumbar vertebra for detecting BMD and the intensity of biomechanics. RESULTS: At the 14th day in experiment, being compared with control group,the BMD of femoral bone, pelvis and lumbar vertebra in model group decreased significantly (P < 0.001, P < 0.001, P < 0.01) and the change of BMD of cranial bone, thoracic vertebra and radioulna in model group was not remarkable (P > 0.05). At the 28th day in experiment, the BMD of femoral bone and lumbar vertebra, the maximal load of femoral bone decreased significantly in model group as compared with control group (P < 0.01, P < 0.001, P < 0.01). CONCLUSION: BMD in vive body showed that suspensory simulated weightlessness for 14 days could cause disorder of bone metabolism and remarkable mineral loss of weight bearing bone, even BMD and biomechanical intensity of weight bearing bone decrease obviously when removing suspension for 14 days. The results suggest that the disorder of bone metabolism could not be recovered in short time.

[Effects of pingyu capsule on signal transduction of rats with chronic stress-induced depression].

OBJECTIVE: To observe the effects of Pingyu capsule on such important regulatory factors as cAMP, PKA and PKC of the signal transduction in rats with chronic stress-induced depression. METHOD: Wistar male rats were randomly divided into control group, model group, paroxetine group, and Pingyu capsule low, middle and high doses groups; rats in all groups but the control group were fed in single cage for 21 days and were given such irritations as lightening stroke on pelma, ice water swimming, pyretic fumigation and tail clipping during this period; lobe cortex and hippocampus of all rats were taken out for detection of the cAMP content by means of radioactive immunization, PKA and PKC content by Elisa, and the PKA and PKC activity by radioactive isotope. RESULT: Content of cAMP in lobe cortex and hippocampus, content and activity of PKA in hippocampus, and content of PKC in lobe cortex of rats in the model group were lower than those in the normal group. Pingyu capsule and paroxetine can increase them. CONCLUSION: The anti-depression effect of Pingyu capsule maybe related to its function of adjusting the signal transduction of cAMP-PKA.

[Effects of Chinese compound prescription on bone metabolism of weightlessness rats simulated by suspension].

OBJECTIVE: To study the effects of Chinese medicine compound on bone metabolism of weightlessness rats simulated by tail suspension. METHOD: Fifty Wistar rats were divided into 5 groups randomly: control group, model group, and low does, medium dose and high does treated group. The experiment period lasted 21 days. After the Chinese compound prescription and distilled water were orally given to treated groups, and control and model group for 7 days, respectively, the tail suspension experiment was performed for treated and model group, meanwhile administration of Chinese compound prescription and distilled water still lasted until the end of the experiment. Blood serum was collected for determination of alkaline phosphatase (ALP), bone gla protein (BGP), tartrate-resistant acid phosphatase (TRAP), femoral bone HOP. The changes of bone mineral density (BMD) of femoral bone and lumbar vertebra were observe. RESULT: Compared with control group, the ALP level of model group was markedly decreased (P < 0.05), no change of BGP, TRAP was not observed, the BMD of femoral bone and lumbar vertebra were decreased remarkably (P < 0.05), Compared with model group, the change of ALP level of treated groups was not significant for all treated groups, the BGP level and BMD for medium dose group were increased (P < 0.05), the TRAP level for medium dose and high does groups was decreased (P < 0.05) CONCLUSION: The Chinese compound prescription can improve the bone formation and prevent bone loss via inhibiting bone absorption and improving ossify, bone mineral deposition and mineralization as well as increasing BMD, which leads to prevention and treatment of bone loss.

[Comparative researches on medicinal property theories of traditional Chinese medicine and traditional Mongolian medicinal herbs].

This article reveals the similarities and differences between the two materia medica systems of traditional Chinese medicine and traditional Mongolian medicine by comparing the medicinal property theories of these two; our expectations are the mutual profits and complementation of the two traditional medicines from each other, a broader clinical use of natural medicinal herbs, and then, a development of traditional medicines.