Pharmaceutical Biology最新文献

{"title":"Extracts of <i>Thesium chinense</i> inhibit SARS-CoV-2 and inflammation <i>in vitro</i>.","authors":"Juncheng Ma,&nbsp;Juanru Wei,&nbsp;Gang Chen,&nbsp;Xiaowei Yan,&nbsp;Hechun Sun,&nbsp;Ning Li","doi":"10.1080/13880209.2023.2253841","DOIUrl":"https://doi.org/10.1080/13880209.2023.2253841","url":null,"abstract":"<p><strong>Context: </strong>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still spreading rapidly. Relevant research based on the antiviral effects of <i>Thesium chinense</i> Turcz (Santalaceae) was not found.</p><p><strong>Objective: </strong>To investigate the antiviral and anti-inflammatory effects of extracts of <i>T. chinense</i>.</p><p><strong>Materials and methods: </strong>To investigate the anti-entry and replication effect of the ethanol extract of <i>T. chinense</i> (drug concentration 80, 160, 320, 640, 960 μg/mL) against the SARS-CoV-2. Remdesivir (20.74 μM) was used as positive control, and Vero cells were used as host cells to detect the expression level of nucleocapsid protein (NP) in the virus by real-time quantitative polymerase chain reaction (RT-PCR) and Western blotting. RAW264.7 cells were used as an anti-inflammatory experimental model under lipopolysaccharide (LPS) induction, and the expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>The ethanol extract of <i>T. chinense</i> significantly inhibited the replication (half maximal effective concentration, EC₅₀: 259.3 μg/mL) and entry (EC₅₀: 359.1 μg/mL) of SARS-CoV-2 into Vero cells, and significantly reduced the levels of IL-6 and TNF-α produced by LPS-stimulated RAW264.7 cells. Petroleum ether (EC₅₀: 163.6 μg/mL), ethyl acetate (EC₅₀: 22.92 μg/mL) and <i>n</i>-butanol (EC₅₀: 56.8 μg/mL) extracts showed weak inhibition of SARS-CoV-2 replication in Vero cells, and reduced the levels of IL-6 and TNF-α produced by LPS-stimulated RAW264.7 cells.</p><p><strong>Conclusion: </strong><i>T. chinense</i> can be a potential candidate to fight SARS-CoV-2, and is becoming a traditional Chinese medicine candidate for treating COVID-19.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"61 1","pages":"1446-1453"},"PeriodicalIF":3.8,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10195017","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":"Effect of Er Miao San on peritoneal macrophage polarisation through the miRNA-33/NLRP3 signalling pathway in a rat model of adjuvant arthritis.","authors":"Min Liu,&nbsp;Xiangwen Meng,&nbsp;Zihua Xuan,&nbsp;Simeng Chen,&nbsp;Jin Wang,&nbsp;Zhiluo Chen,&nbsp;Jiayu Wang,&nbsp;Xiaoyi Jia","doi":"10.1080/13880209.2022.2066700","DOIUrl":"https://doi.org/10.1080/13880209.2022.2066700","url":null,"abstract":"<p><strong>Context: </strong>Er Miao San (EMS) is a formulation that contains <i>Atractylodis Rhizoma</i> and <i>Phellodendri Cortex</i> in 1:1 ratio, and is commonly used to treat rheumatoid arthritis (RA) and other inflammatory diseases.</p><p><strong>Objective: </strong>We investigated the mechanism of action and effects of EMS on peritoneal macrophage differentiation in a rat model of adjuvant arthritis (AA).</p><p><strong>Materials and methods: </strong>EMS (3, 1.5 and 0.75 g/kg; once daily) and methotrexate (0.5 mg/kg; once every 3 days) were administered orally from days 21 to 35 after immunisation. Paw swelling and arthritis index were measured; pathological changes in the ankle joint were observed using x-ray and haematoxylin eosin staining. The ratio of CD86/CD206 in macrophages was detected by flow cytometry. Examination of the miRNA-33/NLRP3 signalling pathway was examined by RT-qPCR and western blotting. The levels of cytokines in the serum and cell supernatants were tested by ELISA.</p><p><strong>Results: </strong>EMS significantly reduced the AA index in rats (from 11.0 to 9.3) and pathological changes in the ankle joint (from 3.8 to 1.4). The ratio of CD86/CD206 was reduced, and polarisation to M1 improved (from 0.9 to 0.6) in macrophages of EMS-treated rats. EMS downregulated the miRNA-33/NLRP3 pathway. Furthermore, EMS treatment increased IL-10 and TGF-β levels in the serum and supernatant of macrophages of AA rats and simultaneously decreased the levels of IL-1β and TNF-α.</p><p><strong>Discussion and conclusions: </strong>Our results suggest that EMS may reduce macrophage polarisation to the M1 inflammatory phenotype by downregulating the miRNA-33/NLRP3 pathway in AA rats. These findings may provide new insights into the treatment of RA.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"60 1","pages":"846-853"},"PeriodicalIF":3.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10510800","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":"60 1","pages":"997-1010"},"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":"60 1","pages":"2229-2236"},"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}

{"title":"Alpinetin suppresses CYP3A4, 2C9, and 2E1 activity <i>in vitro</i>.","authors":"Hongming Song,&nbsp;Chuankui Wei,&nbsp;Wu Yang,&nbsp;Zhaohe Niu,&nbsp;Mingkai Gong,&nbsp;Haiyan Hu,&nbsp;Haibo Wang","doi":"10.1080/13880209.2022.2071450","DOIUrl":"https://doi.org/10.1080/13880209.2022.2071450","url":null,"abstract":"<p><strong>Context: </strong>Alpinetin, the major active constitutes of <i>Alpinia katsumata</i> Hayata (Zingiberaceae), has been demonstrated to possess the activity of anti-breast cancer. Cytochrome P450 enzymes (CYP450s) plays vital roles in the biotransformation of various drugs.</p><p><strong>Objective: </strong>To assess the effect of alpinetin on the activity of CYP450s and estimate the inhibition characteristics.</p><p><strong>Materials and methods: </strong>The activity of CYP450s was evaluated in pooled human liver microsomes with corresponding substrates and marker reactions. The effect of alpinetin was compared with blank control (negative control) and corresponding inhibitors (positive control). The dose-dependent and time-dependent experiments were conducted in the presence of 0, 2.5, 5, 10, 25, 50, and 100 μM alpinetin and incubated for 0, 5, 10, 15, and 30 min.</p><p><strong>Results: </strong>Alpinetin suppressed CYP3A4, 2C9, and 2E1 activity. All the inhibitions were significantly influenced by alpinetin contration with the IC₅₀ values of 8.23 μM (CYP3A4), 12.64 μM (CYP2C9), and 10.97 μM (CYP2E1), respectively. The inhibition of CYP3A4 was fitted with the non-competitive model with a <i>Ki</i> value of 4.09 μM and was time-dependent with <i>KI</i> and <i>Kinact</i> values of 4.67 min and 0.041 μM^-1, respectively. While CYP2C9 and 2E1 were inhibited by alpinetin competitively with <i>Ki</i> values of 6.42 (CYP2C9) and 5.40 μM (CYP2E1), respectively, in a time-independent manner.</p><p><strong>Discussion and conclusion: </strong>The <i>in vitro</i> inhibitory effect of alpineticn on CYP3A, 2C9, and 2E1 implied the potential interaction of alpinetin or its origin herbs with the drugs metabolised by those CYP450s, which needs further <i>in vivo</i> validation.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"60 1","pages":"1032-1037"},"PeriodicalIF":3.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10515495","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":"Antiperspirant effects and mechanism investigation of Mulisan decoction in rats based on plasma metabolomics.","authors":"Shan-Peng Ma,&nbsp;Wei-Ping Ma,&nbsp;Shi-Ning Yin,&nbsp;Xiang-Yue Chen,&nbsp;Xiao-Qing Ma,&nbsp;Bao-Hong Wei,&nbsp;Jing-Guang Lu,&nbsp;Hong-Bing Liu","doi":"10.1080/13880209.2022.2074465","DOIUrl":"https://doi.org/10.1080/13880209.2022.2074465","url":null,"abstract":"<p><strong>Context: </strong>Mulisan decoction (MLS) is a classic formula of traditional Chinese medicine for treating hyperhidrosis. The mechanism remains unclear.</p><p><strong>Objective: </strong>To investigate the antiperspirant effect and underlying mechanisms of MLS.</p><p><strong>Materials and methods: </strong>Fifty rats were divided into control, model, and three doses of MLS intervention groups (<i>n</i> = 10). Rats except for control group were induced diseases features of the applicable scope of MLS <i>via</i> i.p. reserpine (0.5 mg/kg/d) for 10 days. From day 11, MLS groups were administrated orally MLS at 0.6, 3, and 15 g/kg once a day for 14 days, respectively. After the last administration, sweating was induced in all rats <i>via</i> s.c. pilocarpine (25 mg/kg), the right hind foot of rats was stained, and sweat point numbers were observed. Rat serum was collected to detect IL-2, IL-6, IFN-γ, and TNF-α. Rat plasma was collected for endogenous metabolite analysis <i>via</i> UPLC-QE-Focus-MS.</p><p><strong>Results: </strong>Rats treated with MLS presented a significant decrease in sweat point numbers (13.5%), increase in body weight (13.2%), and promotion in the balance of Th1/Th2 cytokine ratio <i>via</i> increasing IL-2 (38.3%), IFN-γ (20.1%), and TNF-α (22.0%) and decreasing IL-6 (24.7%) compared with the model group (<i>p</i> < 0.05). Plasma metabolomics disclosed 15 potential biomarkers related to model rats, of which two could be significantly reversed by MLS (<i>p</i> < 0.05). The involved pathways were pantothenate and CoA biosynthesis, and porphyrin metabolism.</p><p><strong>Conclusions: </strong>MLS demonstrated a good antiperspirant effect and metabolism improvement. These findings inspire more clinical study validation on immune improvement and antiperspirant effect.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"60 1","pages":"1055-1062"},"PeriodicalIF":3.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10515496","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":"60 1","pages":"1095-1105"},"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":"60 1","pages":"1511-1519"},"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":"60 1","pages":"1303-1316"},"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":"Myristicin regulates proliferation and apoptosis in oxidized low-density lipoprotein-stimulated human vascular smooth muscle cells and human umbilical vein endothelial cells by regulating the PI3K/Akt/NF-κB signalling pathway.","authors":"Liang Luo,&nbsp;Huiying Liang,&nbsp;Luoying Liu","doi":"10.1080/13880209.2021.2010775","DOIUrl":"https://doi.org/10.1080/13880209.2021.2010775","url":null,"abstract":"<p><strong>Context: </strong>Atherosclerosis (AS) is a chronic inflammatory disease. Human vascular smooth muscle cell (hVSMC) accumulation and human umbilical vein endothelial cell (HUVEC) dysfunction are associated with the pathogenesis of AS. This study explores whether myristicin plays a protective role in AS.</p><p><strong>Materials and methods: </strong>hVSMCs and HUVECs were stimulated with 100 μg/mL oxidized low-density lipoprotein (ox-LDL) to establish a cellular model of AS. Cell viability, lactate dehydrogenase (LDH) release and cell apoptosis were evaluated using MTT, LDH and flow cytometry assays, respectively. Cell migration and inflammatory cytokine release were assessed using Transwell assay and ELISA.</p><p><strong>Results: </strong>Myristicin (5, 10, 25, and 50 μM) had no obvious effect on cell viability or the activity of LDH in hVSMCs, while 100 and 200 μM myristicin markedly suppressed hVSMCs viability and increased LDH release. Myristicin had no obvious effect on cell viability or the activity of LDH in HUVECs. Myristicin inhibited viability and increased apoptosis in ox-LDL-treated hVSMCs, but was associated with increased proliferation and inhibited apoptosis in HUVECs stimulated by ox-LDL. Additionally, myristicin markedly suppressed ox-LDL-induced hVSMCs migration and the release of inflammatory cytokines, including MCP-1, IL-6, VCAM-1 and ICAM-1, in HUVECs. Results also demonstrated that the promoting effects of ox-LDL on the PI3K/Akt and NF-κB signalling pathway in both hVSMCs and HUVECs were abolished by treatment with myristicin.</p><p><strong>Discussion and conclusions: </strong>Myristicin regulated proliferation and apoptosis by regulating the PI3K/Akt/NF-κB signalling pathway in ox-LDL-stimulated hVSMCs and HUVECs. Thus, myristicin may be used as a new potential drug for AS treatment.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"60 1","pages":"56-64"},"PeriodicalIF":3.8,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8676624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10510291","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}