Pharmaceutical Biology最新文献

Context: Tanzania has rich medicinal plant (MP) resources, and most rural inhabitants rely on traditional healing practices for their primary healthcare needs. However, available research evidence on antimalarial MPs is highly fragmented in the country.

Objective: This systematic review compiles ethnomedicinal research evidence on MPs used by Tanzanians as antimalarials.

Materials and methods: A systematic web search was conducted using various electronic databases and grey materials to gather relevant information on antimalarial MPs utilized by Tanzanians. The review was per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The data were collected from 25 articles, and MS Excel software was used to analyse relevant ethnobotanical information using descriptive statistics.

Results: A total of 227 MPs belonging to 67 botanical families and 180 genera were identified. Fabaceae (15.9%) is the most frequently utilized family. The ethnobotanical recipes analysis indicated leaves (40%) and trees (44%) are the preferred MPs part and life form, respectively. Decoctions (67%) are the dominant preparation method of remedies. Of the recorded MPs, 25.9% have been scientifically investigated for antimalarial activities with positive results. However, 74.1% of MPs have no scientific records on antimalarial activities, but they could be potential sources of remedies.

Conclusions: The study discloses a wealth of antimalarial MPs possessed by Tanzanians and suggests a need for research to authenticate the healing potential of antimalarial compounds from the unstudied MPs. Additionally, it indicates that some of the presented MPs are potential sources for developing safe, effective and affordable antimalarial drugs.

Context: The therapeutic potential of andrographolide is hindered by its poor oral bioavailability and unpredictable pharmacokinetics, primarily due to its limited water solubility.

Objective: This work aimed to enhance the solubility and pharmacokinetics of andrographolide, a bioactive compound in Andrographis paniculata (Burm. f.) Nees (Acanthaceae), using solubilizing agents and a bioenhancer.

Materials and methods: Four groups of beagles were compared: (1) A. paniculata powder alone (control), (2) A. paniculata powder with 50% weight/weight (w/w) β-cyclodextrin solubilizer, (3) A. paniculata powder with 1% w/w sodium dodecyl sulfate (SDS) solubilizer, and (4) A. paniculata powder co-administered with 1% w/w SDS solubilizer and 10% piperine bioenhancer. All groups received a consistent oral dose of 3 mg/kg of andrographolide, administered both as a single dose and multiple doses over seven consecutive days.

Results: Thirteen chemical compounds were identified in A. paniculata powder, including 7 diterpenoids, 5 flavonoids, and 1 phenolic compound. A. paniculata co-administration with either 50% w/w β-cyclodextrin or 1% w/w SDS, alone or in combination with 10% w/w piperine, significantly increased systemic andrographolide exposure by enhancing bioavailability (131.01% to 196.05%) following single and multiple oral co-administration. Glucuronidation is one possible biotransformation pathway for andrographolide, as evidenced by the excretion of glucuronide conjugates in urine and feces.

Conclusion: The combination of solubilizing agents and a bioenhancer improved the oral bioavailability and pharmacokinetics of andrographolide, indicating potential implications for A. paniculata formulations and clinical therapeutic benefits. Further investigation in clinical studies is warranted.

Context: Polyporus polysaccharide (PPS), the leading bioactive ingredient extracted from Polyporus umbellatus (Pers.) Fr. (Polyporaceae), has been demonstrated to exert anti-bladder cancer and immunomodulatory functions in macrophages.

Objective: To explore the effects of homogeneous Polyporus polysaccharide (HPP) on the proliferation and autophagy of bladder cancer cells co-cultured with macrophages.

Materials and methods: MB49 bladder cancer cells and RAW264.7 macrophages were co-cultured with or without HPP intervention (50, 100, or 200 μg/mL) for 24 h. The cell counting kit-8 (CCK-8) assay and 5-ethynyl-2″-deoxyuridine (EdU) staining evaluated MB49 cell proliferation. Monodansylcadaverine (MDC) staining and transmission electron microscopy (TEM) observed autophagosomes. Western blotting detected the expression levels of autophagy-related proteins and PI3K/Akt/mTOR pathway proteins.

Results: HPP inhibited the proliferation of MB49 cells co-cultured with RAW264.7 cells but not MB49 cells alone. HPP altered the expression of autophagy-related proteins and promoted the formation of autophagosomes in MB49 cells in the co-culture system. Autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) not only antagonized HPP-induced autophagy but also attenuated the inhibitory effects of HPP on MB49 cell proliferation in the co-culture system. HPP or RAW264.7 alone was not sufficient to induce autophagy in MB49 cells. In addition, HPP suppressed the protein expression of the PI3K/Akt/mTOR pathway in MB49 cells in the co-culture system.

Discussion and conclusions: HPP induced bladder cancer cell autophagy by regulating macrophages in the co-culture system, resulting in the inhibition of cancer cell proliferation. The PI3K/Akt/mTOR pathway was involved in HPP-induced autophagy in the co-culture system.

Context: Diabetic kidney disease (DKD) is a prominent complication arising from diabetic microangiopathy, and its prevalence and renal impact have placed it as the primary cause of end-stage renal disease. Traditional Chinese Medicine (TCM) has the distinct advantage of multifaceted and multilevel therapeutic attributes that show efficacy in improving clinical symptoms, reducing proteinuria, protecting renal function, and slowing DKD progression. Over recent decades, extensive research has explored the mechanisms of TCM for preventing and managing DKD, with substantial studies that endorse the therapeutic benefits of TCM compounds and single agents in the medical intervention of DKD.

Objective: This review lays the foundation for future evidence-based research efforts and provide a reference point for DKD investigation.

Methods: The relevant literature published in Chinese and English up to 30 June 2023, was sourced from PubMed, Cochrane Library, VIP Database for Chinese Technical Periodicals (VIP), Wanfang Data, CNKI, and China Biology Medicine disc (CBM). The process involved examining and summarizing research on TCM laboratory tests and clinical randomized controlled trials for DKD treatment.

Results and conclusions: The TCM intervention has shown the potential to inhibit the expression of inflammatory cytokines and various growth factors, lower blood glucose levels, and significantly affect insulin resistance, lipid metabolism, and improved renal function. Furthermore, the efficacy of TCM can be optimized by tailoring personalized treatment regimens based on the unique profiles of individual patients. We anticipate further rigorous and comprehensive clinical and foundational investigations into the mechanisms underlying the role of TCM in treating DKD.

Context: The use of traditional Chinese medicine (TCM) for breast cancer patients inhibits tumor cell growth and proliferation, alleviates adverse reactions, and inhibits tumor recurrence and metastasis post-surgery. An assessment of its historical efficacy and an examination of the latest research trends are imperative to thoroughly leverage the potential of TCM for breast cancer treatment.

Objective: This study analyzes the published literature on TCM for breast cancer treatment using bibliometric analysis to determine the current state, identify hot spots, and discern trends, providing insight into research in this field.

Methods: TCM-based breast cancer treatment publications between 2003 and 2022 were retrieved from the Web of Science, China National Knowledge Infrastructure, Wanfang, and Duxiu databases. Visual analysis was performed using VOSviewer (V1.6.19) and CiteSpace (V6.3.R1) software. Examined metrics included the annual publication count, literature and journal, national and institutional contributions, author co-occurrence, keyword co-occurrence, keywords timeline, and keywords with citation bursts in this research field.

Results and conclusion: A total of 1080 English publications and 2617 Chinese publications were included in the analysis. China was the leading contributor of publications. High-frequency keywords such as 'apoptosis', 'expression', 'in vivo', 'chemotherapy', 'triple-negative breast cancer', and 'lymphedema' were identified from English and Chinese publications; 'epithelial mesenchymal transition' and 'network pharmacology' emerged as hotspots. The development of modern science, technology, and in-depth research can result in broader prospects for the research and application of TCM in breast cancer treatment, resulting in more effective solutions for the treatment of breast cancer and other malignant tumors.

Context: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus. Chinese patent medicines (CPMs) are widely used in clinical practice to treat DPN.

Objective: This study aims to summarize the latest evidence on the harms and benefits of CPMs as adjunctive therapy for DPN.

Materials and methods: We conducted searches for randomized controlled trials (RCTs) evaluating CPMs in conjunction with mecobalamin (Mec) or alpha-lipoic acid (αLA) across eight databases up to July 2024. The surface under the cumulative ranking area (SUCRA) was utilized to assess the clinical efficacy rate (CER), the peroneal motor nerve conduction velocity (pMNCV), the peroneal sensory nerve conduction velocity (pSNCV), the median motor nerve conduction velocity (mMNCV), and the median sensory nerve conduction velocity (mSNCV).

Results: The search yielded 128 eligible studies with 31 CPMs with Mec and 39 eligible studies with 17 CPMs with αLA. SUCRA rankings indicated that, when combined with Mec, Mailuoning liquid (lMLN) was the most effective regimen for CER, Honghua injection (iHH) for pMNCV, Maixuekang capsule (cMXK) for pSNCV, Dengzhanxixin injection (iDZXX) for mMNCV, and Tongxinluo capsule (cTXL) for mSNCV. Combined with αLA, Danhong injection (iDH) showed the highest efficacy for CER, pSNCV, and mSNCV, while Xueshuantong injection (iXShT) was the most effective for pMNCV and mMNCV.

Conclusion: This network meta-analysis confirms the efficacy and safety of 37 CPMs combined with Mec or αLA for treating DPN. However, given the potential risk of bias and the very low certainty of the evidence, these recommendations should be adopted with caution.

Context: Tanyu Tongzhi Formula (TTF) exhibits potential against atherosclerosis; however, its mechanisms remain unclear.

Objective: This study explores the pharmacological mechanisms of TTF in treating atherosclerosis.

Materials and methods: Network pharmacology, molecular docking, mendelian randomization (MR), and liquid chromatography-mass spectrometry (LC-MS) analyses were utilized to reveal potential targets and compounds of TTF against atherosclerosis. After exploring the appropriate concentration of TTF to treat HCAECs using Cell Counting Kit-8 (CCK-8), the HCAECs were divided into three groups: control, oxidized low-density lipoprotein (ox-LDL, 50 μg/mL), and ox-LDL (50 μg/mL) + TTF (1 mg/mL). After 24-h incubation, the efficacy of TTF was verified by CCK-8, Oil red O staining, and ELISA. The expression of key targets was detected by real-time polymerase chain reaction (qPCR) and western blotting.

Results: A total of 137 active compounds and 127 potential TTF targets against atherosclerosis were identified. MR identified ALB, TNF, PPARα, and PPARγ as key targets. Molecular docking indicated that baicalin, naringenin, and curcumin exhibited suitable binding activities to these targets, further confirming by LC-MS analysis. The IC₅₀ of TTF in HCAECs was 18.25 mg/mL. TTF treatment significantly improved atherosclerosis by enhancing cell viability, reducing lipid accumulation, and inhibiting inflammation factors (IL6, IL1B and TNF-α) in ox-LDL-treated HCAECs. Moreover, qPCR or western blotting indicated that TTF could up-regulate PPARα and PPARγ while down-regulate TNF expression.

Discussion and conclusions: Our results revealed active compounds, key pathways, and core targets of TTF against atherosclerosis, providing experimental support for its application in treating of atherosclerosis.

Context: Bailing capsule, derived from Cordyceps sinensis (Berk.) Sacc. (Clavicipitaceae), has shown potential in the treatment of chronic obstructive pulmonary disease (COPD), a prevalent respiratory disorder.

Objective: This study elucidates the efficacy and mechanism of action of the use of Bailing capsules in the treatment of COPD using meta-analysis and network pharmacology.

Materials and methods: A meta-analysis of randomized controlled trials (RCTs) was performed. The treatment group received Bailing capsules alongside standard therapy, while the control group received standard therapy or in combination with other traditional Chinese medicines. Efficacy outcomes included lung function, exercise tolerance, acute exacerbation risk, and quality of life. Network pharmacology and molecular docking identified key targets of Bailing capsules.

Results: The meta-analysis of 27 RCTs showed significant improvements in the treatment group for forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, and the 6-min walk test (6MWT). Additionally, there was a marked reduction in acute COPD attacks and an improvement in quality of life. Meanwhile, network pharmacological analysis identified SRC, HIF1A, NFKB1, HDAC2, and PRKACA, as the potential core targets for Bailing capsules in the treatment of COPD.

Discussion and conclusion: Bailing capsules have shown promising results in the treatment of stable COPD. Future studies should focus on large-scale, multicenter RCTs to confirm the long-term benefits and safety of Bailing capsules.

Context: Ulcerative colitis has been clinically treated with Qing Hua Chang Yin (QHCY), a traditional Chinese medicine formula. However, its precise mechanisms in mitigating chronic colitis are largely uncharted.

Objective: To elucidate the therapeutic efficiency of QHCY on chronic colitis and explore its underlying molecular mechanisms.

Materials and methods: A total ion chromatogram fingerprint of QHCY was analysed. Chronic colitis was induced in male C57BL/6 mice using 2% dextran sodium sulphate (DSS) over 49 days. Mice were divided into control, DSS, DSS + QHCY (0.8, 1.6 and 3.2 g/kg/d dose, respectively) and DSS + mesalazine (0.2 g/kg/d) groups (n = 6). Mice were intragastrically administered QHCY or mesalazine for 49 days. The changes of disease activity index (DAI), colon length, colon histomorphology and serum pro-inflammatory factors in mice were observed. RNA sequencing was utilized to identify the differentially expressed transcripts (DETs) in colonic tissues and the associated signalling pathways. The expression of endoplasmic reticulum (ER) stress-related protein and NF-κB signalling pathway-related proteins in colonic tissues was detected by immunohistochemistry staining.

Results: Forty-seven compounds were identified in QHCY. Compared with the DSS group, QHCY significantly improved symptoms of chronic colitis like DAI increase, weight loss, colon shortening and histological damage. It notably reduced serum levels of IL-6, IL-1β and TNF-α. QHCY suppressed the activation of PERK-ATF4-CHOP pathway of ER stress and NF-κB signalling pathways in colonic tissues.

Discussion and conclusions: The findings in this study provide novel insights into the potential of QHCY in treating chronic colitis patients.

Context: Pileostegia tomentella Hand. Mazz (Saxifragaceae) total coumarins (TCPT) show antitumour activity in colorectal cancer (CRC) with unknown mechanism of action. Tumour angiogenesis mediated by exosomes-derived miRNA exhibits the vital regulation of endothelial cell function in metastasis of CRC.

Objective: To investigate the effect of TCPT on exosomal miRNA expression and angiogenesis of CRC cells.

Materials and methods: HT-29-derived exosomes were generated from human CRC cells (HT-29) or either treated with TCPT (100 μg/mL) for 24 h, followed by identification by transmission electron microscope, nanoparticle tracking analysis (NTA) and Western blot. Co-culture experiments for human umbilical vein endothelial cells (HUVECs) and exosomes were performed to detect the uptake of exosomes in HUVECs and its influence on HUVECs cells migration and lumen formation ability. Potential target miRNAs in exosomes were screened out by sequencing technology. Rescue assays of angiogenesis were performed by the transfecting mimics or inhibitors of targeted miRNA into HUVECs.

Results: HT-29-derived exosomes, after TCPT treatment (Exo-TCPT), inhibited the migration and lumen formation of HUVECs, reduced the expression levels of vascular marker (FLT-1, VCAM-1 and VEGFR-2) in HUVECs. Furthermore, the level of miR-375-3p was significantly upregulated in Exo-TCPT. Rescue assays showed that high expression of miR-375-3p in HUVECs inhibited migration and lumen formation abilities, which was consistent with the effects of Exo-TCPT, whereas applying miR-375-3p inhibitors displayed opposite effects.

Discussion and conclusion: TCPT exhibits anti-angiogenesis in CRC, possibly through upregulating exosomal miR-375-3p. Our findings will shed light on new target exosomes miRNA-mediated tumour microenvironment and the therapeutic application of Pileostegia tomentella in CRC.