Pharmaceutical Biology最新文献

{"title":"Jing-an oral liquid alleviates Tourette syndrome via the NMDAR/MAPK/CREB pathway <i>in vivo</i> and <i>in vitro</i>.","authors":"Leying Xi,&nbsp;Xixi Ji,&nbsp;Wenxiu Ji,&nbsp;Yue'e Yang,&nbsp;Yajie Zhang,&nbsp;Hongyan Long","doi":"10.1080/13880209.2022.2116056","DOIUrl":"https://doi.org/10.1080/13880209.2022.2116056","url":null,"abstract":"<p><strong>Context: </strong>Jing-an oral liquid (JA) is a Chinese herbal formula used in the treatment of Tourette syndrome (TS); however, its mechanism is unclear.</p><p><strong>Objective: </strong>To investigate the effects of JA on amino acid neurotransmitters and microglia activation <i>in vivo</i> and <i>in vitro</i>.</p><p><strong>Materials and methods: </strong>Sixty male Sprague-Dawley rats were divided into a control group and 5 TS groups. TS was induced in rats with intraperitoneal injection of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (1 mg/kg) and in BV2 cells with lipopolysaccharide. Control and model rats were administered saline, whereas treatment groups were administered JA (5.18, 10.36, or 20.72 g/kg) or tiapride (a benzamide, 23.5 mg/kg) by gavage once daily for 21 days. Stereotypic behaviour was tested. The levels of <i>N</i>-methyl-d-aspartate receptor (NMDAR)/mitogen-activated protein kinase/cAMP response element-binding protein (CREB)-related proteins in striatum and BV2 cells were measured via western blots. CD11b and IBa1 levels were also measured. Ultra-high-performance liquid-chromatography was used to determine γ-aminobutyric acid (GABA), glutamic acid (Glu), and aspartic acid (ASP) levels.</p><p><strong>Results: </strong>JA markedly alleviated the stereotype behaviour (25.92 ± 0.35 to 13.78 ± 0.47) in rats. It also increased NMDAR1 (0.48 ± 0.09 to 0.67 ± 0.08; 0.54 ± 0.07 to 1.19 ± 0.18) expression and down-regulated the expression of p-ERK, p-JNK, p-P38, and p-CREB in BV2 cells and rat striatum. Additionally, Glu, ASP, GABA, CD11b, and IBa1 levels were significantly decreased by JA.</p><p><strong>Discussion and conclusions: </strong>JA suppressed microglia activation and regulated the levels of amino acid neurotransmitters, indicating that it could be a promising therapeutic agent for TS.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3a/d4/IPHB_60_2116056.PMC9487928.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40357693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of cell cytotoxic activity and molecular mechanism of 5β,19-epoxycucurbita-6,23(<i>E</i>)-diene-3β,19(<i>R</i>),25-triol isolated from <i>Momordica charantia</i> on hepatoma cells.","authors":"Mei-Kang Yuan,&nbsp;Ju-Wen Kao,&nbsp;Wen-Tung Wu,&nbsp;Chiy-Rong Chen,&nbsp;Chi-I Chang,&nbsp;Yu-Jen Wu","doi":"10.1080/13880209.2022.2077766","DOIUrl":"https://doi.org/10.1080/13880209.2022.2077766","url":null,"abstract":"<p><strong>Context: </strong><i>Momordica charantia</i> L. (Cucurbitaceae), known as bitter melon, is an edible fruit cultivated in the tropics. In this study, an active compound, 5β,19-epoxycucurbita-6,23(<i>E</i>)-diene-3β,19(<i>R</i>),25-triol (ECDT), isolated from <i>M. charantia</i> was investigated in regard to its cytotoxic effect on human hepatocellular carcinoma (HCC) cells.</p><p><strong>Objective: </strong>To examine the mechanisms of ECDT-induced apoptosis in HCC cells.</p><p><strong>Materials and methods: </strong>The inhibitive activity of ECDT on HA22T HCC cells was examined by MTT assay, colony formation assay, wound healing assay, TUNEL/DAPI staining, annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining and JC-1 dye. HA22T cells were treated with ECDT (5, 10, 15, 20 and 25 μM) for 24 h, and the molecular mechanism of cells apoptosis was examined by Western blot. Cells treated with vehicle DMSO were used as the negative control.</p><p><strong>Results: </strong>ECDT inhibited the cell proliferation of HA22T cells in a dose-dependent manner. Flow cytometry showed that ECDT treatment at 10-20 μM increased early apoptosis by 10-14% and late apoptosis by 2-5%. Western blot revealed that ECDT treatment activated the mitochondrial-dependent apoptotic pathway, and ECDT-induced apoptosis was mediated by the caspase signalling pathway and activation of JNK and p38MAPK. Pre-treatment of cells with MAPK inhibitors (SB203580 or SP600125) reversed the ECDT-induced cell death, which further supported the involvement of the p38MAPK and JNK pathways.</p><p><strong>Discussion and conclusions: </strong>Our results indicated that ECDT can induce apoptosis through the p38MAPK and JNK pathways in HA22T cells. The findings suggested that ECDT has a valuable anticancer property with the potential to be developed as a new chemotherapeutic agent for the treatment of HCC.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40405426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Qushi Huayu decoction attenuated hepatic lipid accumulation via JAK2/STAT3/CPT-1A-related fatty acid β-oxidation in mice with non-alcoholic steatohepatitis.","authors":"QinMei Sun,&nbsp;Xin Wang,&nbsp;Xin Xin,&nbsp;ZiMing An,&nbsp;YiYang Hu,&nbsp;Qin Feng","doi":"10.1080/13880209.2022.2134898","DOIUrl":"https://doi.org/10.1080/13880209.2022.2134898","url":null,"abstract":"<p><strong>Context: </strong>Qushi Huayu decoction (QHD) has been clinically used for treating non-alcoholic steatohepatits (NASH). However, little is known about the effect of QHD on fatty acid β-oxidation (FAO)-dependent lipid consumption.</p><p><strong>Objective: </strong>To investigate the mechanism of QHD on FAO-related hepatic lipid accumulation.</p><p><strong>Materials and methods: </strong>Male C57BL/6J mice were randomly divided into 5 groups (<i>n</i> = 8): normal diet and drinking water (CON), high-fat and high-carbohydrate diet (HFHC), QHD-L (2.875 g/kg), QHD-H (11.5 g/kg) and obeticholic acid (OCA) (10 mg/kg/day) groups. All mice freely consumed an appropriate diet for 18 weeks, and QHD was orally administered in the last 6 weeks. Measurements of general condition, hepatic histopathology, and JAK2/STAT3 signalling pathway were taken.</p><p><strong>Results: </strong>QHD significantly improved NASH in mice, as reflected by improving serum glucolipid metabolism, decreasing enzymes activities, reducing hepatic triglyceride (HFHC: 70.07 ± 2.81 mg/g; QHD-H: 34.06 ± 5.74 mg/g) and ameliorating hepatic steatosis, inflammation in pathology. Further, both the mRNA and protein level of hepatic CPT-1A (<i>p</i> < 0.05), a rate-limiting enzyme of FAO, increased drastically following QHD treatment. Meanwhile, the content of hepatic ATP (<i>p</i> < 0.05) increased significantly after treatment with QHD. Further mechanistic results revealed that both the total protein and nuclear p-STAT3 in the liver were significantly down-regulated after QHD treatment. The protein level of hepatic p-JAK2 was significantly inhibited by QHD (<i>p</i> < 0.05 or <i>p</i> < 0.01).</p><p><strong>Conclusions: </strong>QHD could attenuate lipid accumulation by increasing JAK2/STAT3/CPT-1A-related FAO, which provides a scientific basis for the clinical application of QHD in treating NASH.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9629123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40654356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of plant iridoids in depression: a review.","authors":"Yaoyao Kou,&nbsp;Zhihao Li,&nbsp;Tong Yang,&nbsp;Xue Shen,&nbsp;Xin Wang,&nbsp;Haopeng Li,&nbsp;Kun Zhou,&nbsp;Luyao Li,&nbsp;Zhaodi Xia,&nbsp;Xiaohui Zheng,&nbsp;Ye Zhao","doi":"10.1080/13880209.2022.2136206","DOIUrl":"https://doi.org/10.1080/13880209.2022.2136206","url":null,"abstract":"<p><strong>Context: </strong>Depression is a mental disorder characterized by low mood, reduced interest, impaired cognitive function, and vegetative symptoms such as sleep disturbances or poor appetite. Iridoids are the active constituents in several Chinese classical antidepressant formulae such as Yueju Pill, Zhi-Zi-Hou-Po Decoction, Zhi-Zi-Chi Decoction, and Baihe Dihuang Decoction. Parallel to their wide usages, iridoids are considered potential lead compounds for the treatment of neurological diseases.</p><p><strong>Objective: </strong>The review summarizes the therapeutic potential and molecular mechanisms of iridoids in the prevention or treatment of depression and contributes to identifying research gaps in iridoids as potential antidepressant medication.</p><p><strong>Methods: </strong>The following key phrases were sought in PubMed, Google Scholar, Web of Science, and China National Knowledge Internet (CNKI) without time limitation to search all relevant articles with <i>in vivo</i> or <i>in vitro</i> experimental studies as comprehensively as possible: ('iridoid' or 'seciridoid' or 'depression'). This review extracted the experimental data on the therapeutic potential and molecular mechanism of plant-derived iridoids for depression.</p><p><strong>Results: </strong>Plant iridoids (i.e., catalpol, geniposide, loganin), and secoiridoids (i.e., morroniside, gentiopicroside, oleuropein, swertiamarin), all showed significant improvement effects on depression.</p><p><strong>Discussion and conclusions: </strong>Iridoids exert antidepressant effects by elevating monoamine neurotransmitters, reducing pro-inflammatory factors, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, increasing brain-derived neurotrophic factor (BDNF) and its receptors, and elevating intestinal microbial abundance. Further detailed studies on the pharmacokinetics, bioavailability, and key molecular targets of iridoids are also required in future research, ultimately to provide improvements to current antidepressant medications.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9621214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40666326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Curcuma longa</i> and <i>Boswellia serrata</i> extract combination for hand osteoarthritis: an open-label pre-post trial.","authors":"Yves Henrotin,&nbsp;Yvan Dierckxsens,&nbsp;Gaëlle Delisse,&nbsp;Nathalie Maes,&nbsp;Adelin Albert","doi":"10.1080/13880209.2022.2147550","DOIUrl":"https://doi.org/10.1080/13880209.2022.2147550","url":null,"abstract":"<p><strong>Context: </strong>Osteoarthritis (OA) of the hand is a common painful musculoskeletal disorder with no cure. There is a need for an efficient and safe treatment to relieve OA pain.</p><p><strong>Objective: </strong>To investigate the effects of a <i>Curcuma longa</i> and <i>Boswellia serrata</i> food supplement in addition to standard care on hand pain.</p><p><strong>Materials and methods: </strong>This open-label, non-controlled, post-observational study was based on 232 patients suffering from hand pain with or without joint deformity. Patients received a medical prescription for a three-month treatment with a food supplement containing 89 mg of <i>C. longa</i> dry extract, 120 mg of <i>B. serrata</i> resin, and 1.8 µg vitamin D. Pain was evaluated on a 10-point visual analog scale (VAS). The number of painful hand joints, patient satisfaction, nonsteroidal anti-inflammatory drugs intake, and side effects were also recorded.</p><p><strong>Results: </strong>Baseline pain intensity (regression coefficient ± <i>SE</i>: -0.19 ± 0.01, <i>p</i> < 0.0001) and the number of painful joints (regression coefficient ± <i>SE</i>: -0.022 ± 0.0029, <i>p</i> < 0.0001) decreased significantly throughout the 3 months treatment period. NSAIDs intake and topical drug application were significantly decreased by 64% (<i>p</i> < 0.0001) and 79% (<i>p</i> < 0.0001) after 12 weeks, respectively. Only 3/239 (1.3%) patients reported side effects probably related to the product. 80.3% were satisfied with the treatment and 75.5% wished to continue treatment.</p><p><strong>Conclusion: </strong>This is the first clinical trial showing that <i>C. longa</i> and <i>B. serrata</i> resin can relieve symptoms in patients with hand osteoarthritis. The study provides useful information for the design of a clinical trial including a broader population.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9704064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40721115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of valerian extract capsule (VEC) on ethanol- and indomethacin-induced gastric mucosa injury and ameliorative effect of VEC on gastrointestinal motility disorder.","authors":"Yuan Feng,&nbsp;Wan Dai,&nbsp;Junyu Ke,&nbsp;Yong Cui,&nbsp;Shuang Li,&nbsp;Jingjing Ma,&nbsp;Wenfeng Guo,&nbsp;Gang Chen,&nbsp;Ning Li,&nbsp;Yanwu Li","doi":"10.1080/13880209.2022.2071449","DOIUrl":"https://doi.org/10.1080/13880209.2022.2071449","url":null,"abstract":"<p><strong>Context: </strong>Valerian extract capsule (VEC) is an effective Chinese patent medicine used for gastrointestinal (GI) diseases.</p><p><strong>Objective: </strong>To investigate the detailed pharmacological activity for VEC clinical effects in GI diseases.</p><p><strong>Materials and methods: </strong>Sprague-Dawley rats were divided into six groups: control, model, and drug-treated (VEC-L, VEC-M, VEC-H, and teprenone). Rats were orally administered VEC (124, 248, 496 mg/kg) and teprenone (21.43 mg/kg) for 3 consecutive days. After 1 h, the five groups (except the control group) were orally given ethanol (10 mL/kg) for 1 h or indomethacin (80 mg/kg) for 7 h. The spasmolytic activity of VEC (0.01-1 mg/mL) on ACh/BaCl₂-induced New Zealand rabbit smooth muscle contraction was performed. The C57BL/6 mice carbon propelling test evaluated the effects of VEC (248-992 mg/kg) on intestinal motility in normal and neostigmine/adrenaline-induced mice.</p><p><strong>Results: </strong>Compared with the model group, VEC treatment reduced the gastric lesion index and mucosal damage. Further experiments showed that the pathological ameliorative effect of VEC was accompanied by augmentation of the enzymatic antioxidant system and cytoprotective marker (COX-1, <i>p</i> < 0.01; PGI2 <i>p</i> < 0.05;), along with the alleviation of the levels of MPO (ethanol: 15.56 ± 0.82 vs. 12.15 ± 2.60, <i>p</i> < 0.01; indomethacin: 9.65 ± 3.06 vs. 6.36 ± 2.43, <i>p</i> < 0.05), MDA (ethanol: 1.66 ± 0.44 vs. 0.81 ± 0.58, <i>p</i> < 0.01; indomethacin: 1.71 ± 0.87 vs. 1.09 ± 0.43, <i>p</i> < 0.05), and inflammatory mediators. VEC decreased the high tone induced by ACh/BaCl₂ and promoted intestinal transit in normal and neostigmine/adrenaline-induced mice.</p><p><strong>Discussion and conclusions: </strong>VEC showed a potential gastroprotective effect, suggesting that VEC is a promising phytomedicine for the treatment of GI diseases.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9f/30/IPHB_60_2071449.PMC9176630.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9073316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiproliferative and cytotoxic effects of sesquiterpene lactones isolated from <i>Ambrosia artemisiifolia</i> on human adenocarcinoma and normal cell lines.","authors":"Balázs Kovács,&nbsp;Nikoletta Szemerédi,&nbsp;Norbert Kúsz,&nbsp;Tivadar Kiss,&nbsp;Boglárka Csupor-Löffler,&nbsp;Yu-Chi Tsai,&nbsp;Bálint Rácz,&nbsp;Gabriella Spengler,&nbsp;Dezső Csupor","doi":"10.1080/13880209.2022.2103574","DOIUrl":"https://doi.org/10.1080/13880209.2022.2103574","url":null,"abstract":"<p><strong>Context: </strong><i>Ambrosia artemisiifolia</i> L. (Asteraceae) contains sesquiterpene lactones as characteristic secondary metabolites. Many of these compounds exert antiproliferative and cytotoxic effects.</p><p><strong>Objective: </strong>To isolate the sesquiterpene lactones from the aerial part of <i>A. artemisiifolia</i> and to elucidate their cytotoxic, antiproliferative and antibacterial effects.</p><p><strong>Materials and methods: </strong>The compounds were identified by one-dimensional (1D) and 2D NMR, HR-MS spectroscopy from the methanol extract. Isolated compounds were investigated for their cytotoxic and antiproliferative effects on human colonic adenocarcinoma cell lines and human embryonal lung fibroblast cell line using MTT assay. The selectivity of the sesquiterpenes was calculated towards the normal cell line. To check the effect of drug interactions between compounds and doxorubicin, multidrug-resistant Colo 320 cells were used.</p><p><strong>Results: </strong>A new <i>seco</i>-psilostachyinolide derivative, 1,10-dihydro-1'-noraltamisin, and seven known compounds were isolated from the methanol extract. Acetoxydihydrodamsin had the most potent cytotoxic effect on sensitive (Colo205) cell line (IC₅₀ = 7.64 µM), also the strongest antiproliferative effect on Colo205 (IC₅₀ = 5.14 µM) and Colo320 (IC₅₀ = 3.67 µM) cell lines. 1'-Noraltamisin (IC₅₀ = 8.78 µM) and psilostachyin (IC₅₀ = 5.29 µM) showed significant antiproliferative effects on the multidrug-resistant Colo320 cell line and had moderate selectivity against human embryonal lung fibroblast cell line. Psilostachyin C exhibited cytotoxic effects on Colo205 cells (IC₅₀ = 26.60 µM). None of the isolated compounds inhibited ABCB1 efflux pump (EP; P-glycoprotein) or the bacterial EPs.</p><p><strong>Discussion and conclusions: </strong>Acetoxydihydrodamsin, 1'-noraltamisin, and psilostachyin showed the most remarkable cytotoxic and antiproliferative activity on tumour cell lines and exerted selectivity towards MRC-5 cell line.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9344380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Morinda officinalis</i> polysaccharide enable suppression of osteoclastic differentiation by exosomes derived from rat mesenchymal stem cells.","authors":"Peiyu Wu,&nbsp;Feng Jiao,&nbsp;He Huang,&nbsp;Donghua Liu,&nbsp;Wang Tang,&nbsp;Jie Liang,&nbsp;Wen Chen","doi":"10.1080/13880209.2022.2093385","DOIUrl":"https://doi.org/10.1080/13880209.2022.2093385","url":null,"abstract":"<p><strong>Context: </strong><i>Morinda officinalis</i> F.C. How. (MO) (Rubiaceae) can strengthen bone function.</p><p><strong>Objective: </strong>To examine the functional mechanism and effect of MO polysaccharides (MOPs) in rats with glucocorticoid-induced osteoporosis (GIOP).</p><p><strong>Materials and methods: </strong>Rats with GIOP were treated with 5, 15 or 45 mL/kg of MOP [<i>n</i> = 15 for each dose, intraperitoneal (i.p.) injection every other day for 8 weeks]. The body weight of rats and histomorphology of bone tissues were examined. Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (Exo) were collected and identified. Bone marrow-derived macrophages (BMMs) were induced to differentiate into osteoclasts and treated with BMSC-Exo for <i>in vitro</i> studies.</p><p><strong>Results: </strong>MOP reduced the body weight (5, 15, or 45 mg/kg MOP vs. phosphate-buffered saline: 8%, 15% and 25%, <i>p</i> < 0.01), elevated the bone volume to tissue volume (BV/TV), mean trabecular thickness (Tb.Th), mean trabecular number (Tb.N) and mean connectivity density (Conn.D) (40-86%, <i>p</i> < 0.01), decreased the mean trabecular separation/spacing (Tb.Sp) (22-37%, <i>p</i> < 0.01), increased the cortical bone continuity (35-90%, <i>p</i> < 0.01) and elevated RUNX family transcription factor 2 and RANK levels (5-12%, <i>p</i> < 0.01), but suppressed matrix metallopeptidase 9 and cathepsin K levels (9-20%, <i>p</i> < 0.01) in femur tissues. BMSC-Exo from MOP-treated rats (MOP-Exo) suppressed osteoclastic differentiation and proliferation of BMMs. The downregulation of microRNA-101-3p (miR-101-3p) or the upregulation of prostaglandin-endoperoxide synthase 2 (PTGS2) blocked the functions of MOP-Exo.</p><p><strong>Discussion and conclusions: </strong>MOP inhibits osteoclastic differentiation and could potentially be used for osteoporosis management. This suppression may be enhanced by the upregulation of miR-101-3p or the inhibition of PTGS2.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e4/18/IPHB_60_2093385.PMC9272931.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10860520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the mechanism of lupenone for treating type 2 diabetes by integrating pharmacological evaluation and network pharmacology.","authors":"Feng Xu,&nbsp;Mei Zhang,&nbsp;Hongmei Wu,&nbsp;Yuanmin Wang,&nbsp;Ye Yang,&nbsp;Xiangpei Wang","doi":"10.1080/13880209.2022.2067568","DOIUrl":"https://doi.org/10.1080/13880209.2022.2067568","url":null,"abstract":"<p><strong>Context: </strong>Lupenone (LUP) is the active ingredient of <i>Musa basjoo</i> Sieb. et Zucc. (Musaceae) with antidiabetes effects, but an unclear underlying mechanism of action.</p><p><strong>Objective: </strong>Animal experiments combined with network pharmacology were used to explore the mechanism of LUP for treating diabetes.</p><p><strong>Materials and methods: </strong>Insulin resistance (IR) in male Sprague-Dawley rats with type 2 diabetic was induced using a high-fat diet and streptozotocin. The selected rats were divided into normal group, model group, positive group and LUP (2.0, 4.0 and 8.0 mg/kg) groups, and orally administrated twice daily with Tween 80, rosiglitazone or LUP. Fasting blood glucose (FBG), oxidative stress index, blood lipids and IR-related targets were detected. A network pharmacology analysis was performed.</p><p><strong>Results: </strong>Compared to the model group, LUP (8.0 mg/kg) significantly decreased the levels of FBG (22.3%), LEP (9.5%), HbA1c (14.9%) and MDA (12.3%), increased the ADPN (24.2%) levels and GSH-PX activity (12.4%) (<i>p</i> < 0.05), improved oxidative stress, lipid metabolism disorders and pancreas pathological changes, increased the mRNA and protein expression of InsR (3.7-fold and 1.3-fold), IRS-1 (3-fold and 2-fold), IRS-2 (2-fold and 1.6-fold), GLUT-4 (2-fold and 2.4-fold) in skeletal muscle and IRS-1 (6-fold and 1.6-fold), IRS-2 (5.8-fold and 1.5-fold), GLUT-4 (2.5-fold and 1.7-fold) and PPAR-γ (7-fold and 1.4-fold) in adipose tissue (<i>p</i> < 0.05). Network pharmacology analysis revealed that LUP improves IR by multiple targets and signal pathways.</p><p><strong>Conclusions: </strong>The mechanism of LUP for treating diabetes is related to improving IR. LUP has the potential to be developed as a new drug for treating type 2 diabetes.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10509071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rb1 reduces oxidative/carbonyl stress damage and ameliorates inflammation in the lung of streptozotocin-induced diabetic rats.","authors":"Hao Su,&nbsp;Cheng-Ju Tian,&nbsp;Ying Wang,&nbsp;Jiaojiao Shi,&nbsp;Xiaoxiao Chen,&nbsp;Zhong Zhen,&nbsp;Yu Bai,&nbsp;Lan Deng,&nbsp;Chunpeng Feng,&nbsp;Zhuang Ma,&nbsp;Jinfeng Liu","doi":"10.1080/13880209.2022.2140168","DOIUrl":"https://doi.org/10.1080/13880209.2022.2140168","url":null,"abstract":"<p><strong>Context: </strong>Ginsenoside Rb1 (Rb1) is a biologically active component of ginseng [<i>Panax ginseng</i> C.A. Meyer (Araliaceae)].</p><p><strong>Objective: </strong>This study determined the underlying mechanisms of Rb1 treatment that acted on diabetes-injured lungs in diabetic rats.</p><p><strong>Materials and methods: </strong>Streptozotocin (STZ)-induced diabetic rat model was used. Male Sprague-Dawley (SD) rats were divided into four groups (<i>n</i> = 10): control, Rb1 (20 mg/kg), insulin (15 U/kg to attain the euglycaemic state) and diabetic (untreated). After treatment for six weeks, oxidative stress assay; histological and ultrastructure analyses; TNF-α, TGF-β, IL-1 and IL-6 protein expression analyses; and the detection of apoptosis were performed.</p><p><strong>Results: </strong>There was decreased activity of SOD (3.53-fold), CAT (2.55-fold) and GSH (1.63-fold) and increased levels of NO (4.47-fold) and MDA (3.86-fold) in the diabetic group from control. Rb1 treatment increased SOD (2.4-fold), CAT (1.9-fold) and GSH (1.29-fold) and decreased the levels of NO (1.76-fold) and MDA (1.51-fold) as compared with diabetic rats. The expression of IL-6 (5.13-fold), IL-1α (2.35-fold), TNF-α (2.35-fold) and TGF-β (2.39-fold) was increased in diabetic rats from control. IL-6 (2.43-fold), IL-1α (2.27-fold), TNF-α (1.68-fold) and TGF-β (2.3-fold) were decreased in the Rb1 treatment group. Diabetes increased the apoptosis rate (2.23-fold vs. control), and Rb1 treatment decreased the apoptosis rate (1.73-fold vs. the diabetic rats). Rb1 and insulin ameliorated lung tissue injury.</p><p><strong>Discussion and conclusions: </strong>These findings indicate that Rb1 could be useful for mitigating oxidative damage and inflammatory infiltration in the diabetic lung.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9662009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10512391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}