Pharmaceutical Biology最新文献

Context: Epigallocatechin-3-gallate (EGCG), the predominant catechin in green tea, has shown the potential to combat various types of cancer cells through its ability to modulate multiple signaling pathways. However, its low bioavailability and rapid degradation hinder its clinical application.

Objective: This review explores the potential of nanoencapsulation to enhance the stability, bioavailability, and therapeutic efficacy of EGCG in cancer treatment.

Methods: We searched the PubMed database from 2019 to the present, using 'epigallocatechin gallate', 'EGCG', and 'nanoparticles' as search terms to identify pertinent literature. This review examines recent nano-engineering technology advancements that encapsulate EGCG within various nanocarriers. The focus was on evaluating the types of nanoparticles used, their synthesis methods, and the technologies applied to optimize drug delivery, diagnostic capabilities, and therapeutic outcomes.

Results: Nanoparticles improve the physicochemical stability and pharmacokinetics of EGCG, leading to enhanced therapeutic outcomes in cancer treatment. Nanoencapsulation allows for targeted drug delivery, controlled release, enhanced cellular uptake, and reduced premature degradation of EGCG. The studies highlighted include those where EGCG-loaded nanoparticles significantly inhibited tumor growth in various models, demonstrating enhanced penetration and efficacy through active targeting mechanisms.

Conclusions: Nanoencapsulation of EGCG represents a promising approach in oncology, offering multiple therapeutic benefits over its unencapsulated form. Although the results so far are promising, further research is necessary to fully optimize the design of these nanosystems to ensure their safety, efficacy, and clinical viability.

Context: Achyranthes bidentata Blume (ABB), a plant of Amaranthaceae family, has been one of the more commonly used phytomedicine remedies for thousands of years, and recent studies have highlighted the efficacy of its extracts in the treatment of osteoporosis. Nonetheless, a thorough analysis of its benefits is currently absent.

Objective: This meta-analysis assessed the effects of ABB root extract (ABBRE) on osteoporotic rats and provides a rationale for future clinical studies.

Methods: Searches were conducted in seven different Chinese and English databases, and the search period was from their establishment to January 2024. This study was registered in PROSPERO (CRD42023418917). Selected research regarding the ABBRE treatment of osteoporotic rats, and the corresponding research has distinctly reported outcomes, and the data on the bone mineral density (BMD), bone histomorphometrics, biomechanical parameters, and bone biochemical markers of osteoporotic rats can be extracted.

Results: Through screening, 11 studies met the eligibility requirements for inclusion, in which 222 animals were studied. The treatment group with ABBRE exhibited increased bone mineral density (standardized mean difference [SMD] = 1.64, 95% CI = 0.52 to 2.77). Based on subgroup analysis, the greatest increase in bone mineral density was observed when the dose of ABBRE was ≤ 400 mg/kg/day and the duration of treatment was ≤ 12 weeks.

Conclusions: ABBRE is a phytomedicine that can effectively promote the enhancement of bone mineral density and ease osteoporosis. It can be developed into a new alternative therapy by conducting experiments and clinical studies on larger samples.

Context: Ulcerative colitis (UC) is an intractable inflammatory bowel disease that threatens the health of patients. The limited availability of therapeutic strategies makes it imperative to explore more efficient and safer drugs. Indigo naturalis (IN) is a traditional Chinese medicine that possesses many pharmacological activities, including anti-inflammatory, antioxidant, and immunomodulatory activities. The treatment potential of IN for UC has been proven by numerous preclinical and clinical studies in recent years.

Objective: This article provides a comprehensive review of the utility and potential of IN in the treatment of UC.

Methods: 'Indigo naturalis' 'Qing dai' 'Qingdai' 'Ulcerative colitis' and 'UC' are used as the keywords, and the relevant literature is collected from online databases (Elsevier, PubMed, and Web of Science).

Results and conclusion: Indirubin, indigo, isatin, tryptanthrin, and β-sitosterol are considered the key components in the treatment of UC with IN. Both preclinical and clinical studies support the efficacy of IN for UC, especially in severe UC or in those who do not respond to or have poor efficacy with existing therapies. The mechanisms of IN for UC are associated with the aryl hydrocarbon receptor pathway activation, immune regulation, oxidative stress inhibition, and intestinal microbial modulation. However, the clinical use of IN has the risks of adverse events such as pulmonary hypertension, which suggests the necessity for its rational application. As a potential therapeutic agent for UC that is currently receiving more attention, the clinical value of IN has been initially demonstrated and warrants further evaluation.

Context: Coix [Coix lacryma-jobi L. var. mayuen (Roman.) Stapf (Poaceae)], a crop of medicinal and edible significance, contains coixol, which has demonstrated anticancer properties. However, the limited solubility of coixol restricts its potential therapeutic applications.

Objective: This study prepared a water-soluble coixol-β-cyclodextrin polymer (CDP) inclusion compound and evaluated its anticancer effect.

Materials and methods: The coixol-CDP compound was synthesized through a solvent-stirring and freeze-drying technique. Its coixol content was quantified using HPLC, and its stability was tested under various conditions. The anticancer effects of the coixol-CDP compound (4.129, 8.259, 16.518, and 33.035 mg/L for 24, 48, and 72 h) on the proliferation of non-small cell lung cancer (NSCLC) A549 cells were evaluated using an MTT assay; cell morphology was examined by Hoechst nuclear staining; apoptosis and cell cycle was detected by flow cytometry; and the expression of apoptosis-related proteins was assessed by Western blots.

Results: The water-soluble coixol-CDP inclusion compound was successfully prepared with an inclusion ratio of 86.6% and an inclusion yield rate of 84.1%. The coixol content of the compound was 5.63% and the compound remained stable under various conditions. Compared to coixol alone, all 24, 48, and 72 h administrations with the coixol-CDP compound exhibited lower IC₅₀ values (33.93 ± 2.28, 16.80 ± 1.46, and 6.93 ± 0.83 mg/L) in A549 cells; the compound also showed stronger regulatory effects on apoptosis-related proteins.

Discussion and conclusions: These findings offer a new perspective for the potential clinical application of Coix in NSCLC therapy and its future research.

Context: Diabetic peripheral neuropathy (DPN) results in an enormous burden and reduces the quality of life for patients. Considering there is no specific drug for the management of DPN, traditional Chinese medicine (TCM) has increasingly drawn attention of clinicians and researchers around the world due to its characteristics of multiple targets, active components, and exemplary safety.

Objective: To summarize the current status of TCM in the treatment of DPN and provide directions for novel drug development, the clinical effects and potential mechanisms of TCM used in treating DPN were comprehensively reviewed.

Methods: Existing evidence on TCM interventions for DPN was screened from databases such as PubMed, the Cochrane Neuromuscular Disease Group Specialized Register (CENTRAL), and the Chinese National Knowledge Infrastructure Database (CNKI). The focus was on summarizing and analyzing representative preclinical and clinical TCM studies published before 2023.

Results: This review identified the ameliorative effects of about 22 single herbal extracts, more than 30 herbal compound prescriptions, and four Chinese patent medicines on DPN in preclinical and clinical research. The latest advances in the mechanism highlight that TCM exerts its beneficial effects on DPN by inhibiting inflammation, oxidative stress and apoptosis, endoplasmic reticulum stress and improving mitochondrial function.

Conclusions: TCM has shown the power latent capacity in treating DPN. It is proposed that more large-scale and multi-center randomized controlled clinical trials and fundamental experiments should be conducted to further verify these findings.

Context: Pancreatic ductal adenocarcinoma (PDAC), which is characterized by its malignant nature, presents challenges for early detection and is associated with a poor prognosis. Any strategy that can interfere with the beginning or earlier stage of PDAC greatly delays disease progression. In response to this intractable problem, the exploration of new drugs is critical to reduce the incidence of PDAC.

Objective: In this study, we summarize the mechanisms of pancreatitis-induced PDAC and traditional Chinese medicine (TCM) theory and review the roles and mechanisms of botanical drugs and their natural compounds that can inhibit the process of pancreatitis-induced PDAC.

Methods: With the keywords 'chronic pancreatitis', 'TCM', 'Chinese medicinal formulae', 'natural compounds', 'PDAC' and 'pancreatic cancer', we conducted an extensive literature search of the PubMed, Web of Science, and other databases to identify studies that effectively prevent PDAC in complex inflammatory microenvironments.

Results: We summarized the mechanism of pancreatitis-induced PDAC. Persistent inflammatory microenvironments cause multiple changes in the pancreas itself, including tissue damage, abnormal cell differentiation, and even gene mutation. According to TCM, pancreatitis-induced PDAC is the process of 'dampness-heat obstructing the spleen and deficiency due to stagnation' induced by a variety of pathological factors. A variety of botanical drugs and their natural compounds, such as Chaihu classical formulae, flavonoids, phenolics, terpenoids, etc., may be potential drugs to interfere with the development of PDAC via reshaping the inflammatory microenvironment by improving tissue injury and pancreatic fibrosis.

Conclusions: Botanical drugs and their natural compounds show great potential for preventing PDAC in complex inflammatory microenvironments.

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: 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.