Advances in Pharmacological and Pharmaceutical Sciences最新文献

Obesity is a global health concern, steadily rising and posing risks to various health conditions. Despite available antiobesity drugs, their withdrawal due to severe side effects highlights the need for safer alternatives. Natural products, particularly mixed herbal formulations, present a promising avenue in obesity research. This study aimed to investigate the potential antiobesity effects of the NL herbal formula, a traditional remedy in Nakhon Si Thammarat, Thailand, composed of nine herbs. The specific focus was on the inhibitory effects on α-glucosidase and pancreatic lipase enzyme activities, adipogenesis inhibition and lipolysis promotion. NL extract was phytochemically analyzed and assessed for its inhibitory effects on α-glucosidase and pancreatic lipase. Its impact on lipid accumulation and glycerol release was also evaluated. Phytochemical analysis using liquid chromatography-tandem mass spectrometry (LC/MS-MS) identified piperine as the major compound in the NL extract. NL extract exhibited significant inhibition of α-glucosidase, moderate pancreatic lipase inhibition, and dose-dependent reduction in fat accumulation and triglyceride content. Glycerol release increased compared to the control, indicating potential benefits in weight management. This research underscores the potential of the NL formula in combating obesity through its effects on adipogenesis, lipolysis, and enzyme activities. Further investigations into the molecular mechanisms are warranted to fully elucidate its therapeutic potential.

Saikosaponin-b2 (SS-b2), an active ingredient derived from the root of Radix Bupleuri, possesses antitumour, anti-inflammatory, antioxidative and hepatoprotective properties. We investigated the inhibition of tumour proliferation by SS-b2 and the underlying molecular mechanisms, including the MACC1/p-c-Met/p-Akt pathway expression in HepG2 liver cancer cells and H22 tumour-bearing mice. Animal experiments showed that SS-b2 significantly decreased the levels of MACC1, p-c-MET and p-Akt in tumour tissue transplanted with H22 liver cancer cells in mice, while it increased the expression of p-BAD. The results also revealed a concentration-dependent suppression of MACC1, p-c-Met and p-Akt expression in the SS-b2 treatment group compared with the control group. Additionally, the suppression of MACC1 activation by SS-b2 resulted in a reduction in the viability and proliferation of HepG2 liver cancer cells, and this reduction was comparable to that by doxorubicin (DOX). This suggests that SS-b2 has significant efficacy in liver cancer, comparable to DOX. Meanwhile, Annexin V-FITC/PI staining and western blot analysis of cleaved caspase 9 and cleaved caspase 3 demonstrated that SS-b2 induced apoptosis of HepG2 liver cancer cells. These findings provide experimental evidence suggesting that SS-b2 is a promising anticancer agent for liver cancer.

Recent considerations of natural sources as potential anticancer agents have arisen due to the origins of numerous drugs commonly used in chemotherapy. Plant-based drugs, in particular, have attracted attention for offering the advantage of low adverse effects. Among these, the black mulberry plant (Morus nigra L.) stands out as a natural source of polyphenols, widely used to treat metabolic dysfunctions and confer benefits on human health. This study explores the potential of this plant as an anticancer agent, examining its effectiveness based on the type of application of the plant extracts or isolated substances, extraction methods, and its potential biological effects on cancer cells. Consequently, this study contributes to a better understanding of the distribution of phytochemicals in M. nigra and their applications in the context of cancer field. Among the compounds found in black mulberry are flavonoids, chlorogenic acid, cryptochlorogenic acid, and protocatechuic acid, along with cyanidin-3-O-glucoside as the main anthocyanin on the fruit. The phytochemicals derived from M. nigra exhibit antinociceptive and antimicrobial activities, while also showing protective effects, such as antioxidant properties that underline their potential as anticancer agents. The black mulberry's roots, stem bark, pulp, and leaves are particularly rich sources of anti-inflammatory compounds. Ethanol and methanol extraction methods appear to be the most effective in cancer management, offering compounds that facilitate the integration of apoptosis induction, cell growth inhibition, and cytotoxicity modulation. These results collectively represent the salient biological attributes that positioned black mulberry as a promising anticancer agent. Therefore, these findings highlight the multifaceted potential of M. nigra as an anticancer agent, making a compelling case for further research to advance prospects in the medical field.

Oxidative stress is a primary contributor to cerebral ischemia/reperfusion (CI/R) injury, and the use of antioxidants represents a crucial therapeutic strategy for managing CI/R injury. This study aims to explore the antioxidant effects of benzyl ferulate on CI/R injury and elucidate its underlying mechanisms. In vivo models of CI/R injury and hypoxia/reoxygenation (H/R) injury in SH-SY5Y cells were established, followed by treatment with benzyl ferulate. The extent of oxidative stress was assessed through evaluations of neurobiological function, cerebral infarct volume, reactive oxygen species (ROS), apoptosis levels, etc. Results indicated that benzyl ferulate significantly downregulated the expression of NADPH oxidase 2 (NOX) 2/NOX4 while upregulating miRNAs (652/532/92b) in CI/R rats or SH-SY5Y cells. It also reduced total NOX enzyme activity, enhanced superoxide dismutase (SOD) activity, decreased ROS and malondialdehyde (MDA) production, and inhibited cleaved caspase-3 and Bax expression-ultimately leading to reduced cell apoptosis. Benzyl ferulate effectively mitigates oxidative stress injuries of middle cerebral artery occlusion (MCAO) rats or SH-SY5Y cells subjected to H/R, and its mechanism appears to involve modulation of the miRNAs (652/532/92b)/NOX2/4 axis. This study first proved that benzyl ferulate is a promising antioxidant candidate for treating CI/R injury.

Colorectal cancer (CRC) is a multifactorial disease driven by genetic and epigenetic alterations that modulate specific metabolic pathways. Despite the availability of effective treatments like 5-fluorouracil (5-FU), pharmacological therapy for CRC still faces significant challenges, including drug resistance, toxicity, and limited specificity. Therefore, discovering new compounds remains critical to overcoming these barriers and expanding treatment options. This study evaluated the cytotoxicity of fluorinated quaternary ammonium salts (FQAS) library in CRC-derived cell lines with premetastatic and metastatic phenotypes. The genetic and epigenetic background of the CRC cell lines and the selectivity of cytotoxicity compared to nontumor cells and between different CRC stages were also assessed. Additionally, the in silico pharmacological properties of these FQASs were analyzed. Results showed that FQASs 9-14 exhibited significant cytotoxic activity against both premetastatic and metastatic CRC cell lines, with FQASs 9, 13, and 14 displaying selective toxicity toward CRC cells over normal murine colorectal cells. However, in silico studies indicated poor oral bioavailability for these compounds, suggesting that an injection-based delivery route may be more effective for targeting CRC cells. In conclusion, CF₃-containing FQASs are promising therapeutic candidates for CRC treatment.

Pinocembrin (PCB), a flavonoid known for its anti-inflammatory properties, has been approved for various clinical trial applications. To evaluate deeper into the anti-inflammatory potential of the specific enantiomer of natural PCB, we conducted the first investigation into the efficacy of the pure enantiomer (2S)-PCB in modulating inflammatory mediators induced by lipopolysaccharide (LPS) in both murine RAW 264.7 and human U937 macrophage cell lines. This particular compound was isolated from Goniothalamus macrophyllus (Annonaceae), a native plant of Indonesia. This plant has been used traditionally as an herbal medicine to alleviate inflammation. (2S)-PCB was isolated from the stem bark of G. macrophyllus by defatting with n-hexane followed by maceration with methanol. Purification was performed using several chromatographic techniques. The absolute configuration was determined using electronic circular dichroism (ECD) spectroscopy. This compound was then tested for its inhibitory activity on prostaglandin E₂ (PGE₂) and subjected to docking simulations. The results indicated that (2S)-PCB significantly suppressed the production of PGE₂ induced by LPS in both RAW 264.7 and U937 cell lines. The docking simulations revealed that (2S)-PCB reduced PGE₂ levels by suppressing mitogen-activated protein kinase (MAPK) activation through inhibiting p38 and extracellular signal-regulated kinases (ERK). These findings suggest that the compound may prevent worsening of septic shock caused by bacterial infection.

Tea is a rich source of phytochemicals; their composition in tea extracts varies depending on the cultivar, climate, production region, and processing and handling processes. The method of extraction plays a crucial role in determining the biological effects of the bioactive compounds in tea leaves. However, reports on the catechin profiles and antioxidant activities of the extracts obtained from leaves at different stages of maturity are limited. Here, we aimed to evaluate the effect of ultrasound-assisted extraction (UAE) and different drying methods, freeze drying (FD) and spray drying (SD), on the composition of bioactive compounds, phenolic composition, and antioxidant activity of extracts obtained from different part of leaves, top (TT), middle (ML), and mature (MT), of Assam tea cultivar (Camellia sinensis var. assamica) cultivated in Thailand (Thai Assam tea). High-performance liquid chromatography analysis showed that the extracts obtained by UAE with FD from TT leaves (UAEFD-TT) had the highest catechins (341.38 ± 0.11 mg/g extract) and caffeine (93.20 ± 0.36 mg CF/g extract) contents compared with those extracted from ML and MT using the same method as well those obtained by SD. The total phenolic and total flavonoid contents were the highest in UAEFD-TT extracts (456.78 ± 4.31 mg GAE/g extract and 333.98 ± 0.83 mg QE/g extract, respectively). In addition, UAEFD-TT exhibited the highest antioxidant activity; the IC₅₀ values obtained by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays were 1.31 ± 0.02 and 7.51 ± 0.03 μg/mL, respectively. In the ferric-reducing antioxidant power (FRAP) assay, the UAEFD-TT extract demonstrated the highest antioxidant activity (324.54 ± 3.33 μM FeSO₄/mg extract). These results suggest that extraction from TT using UAE followed by FD produced the highest amount of antioxidant compounds in Thai Assam tea extracts.

Background/Aims: Long-term acid suppression with proton pump inhibitors (PPI) leads to hypochlorhydria and facilitates the growth of bacterial flora in the small intestine. Novel acid-suppressants called potassium-competitive acid blockers (P-CABs) seem to be superior to PPIs. However, data on the risk of small intestinal bacterial overgrowth (SIBO) in patients taking P-CABs are limited. Method: We retrospectively analyzed a consecutive series of patients with long-term acid-suppressant (PPIs or P-CABs) use for gastroesophageal reflux disease or nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. All of them underwent endoscopic examinations and Helicobacter pylori testing and took PPIs or P-CABs for at least 3 months. Glucose hydrogen breath tests (GBT) were performed to check for SIBO, and newly developed SIBO-related symptoms including bloating, postprandial discomfort, diarrheas, and constipation, were evaluated. Results: A total of 142 patients were enrolled. Six patients were excluded due to equivocal Helicobacter pylori infection results. The frequency of positive GBTs was 31.7% (25/79) for PPI and 22.8% (13/57) for P-CAB use (p=0.15). Regarding GBT positivity, age-related factor was found to be significant in multivariate analysis (p=0.02). The results of multivariate analysis in cases of SIBO-related symptoms showed that GBT positivity and PPI use were significant (p < 0.01). Conclusion: Long-term use of gastric acid suppressants resulted in positive GBT in approximately 30% of patients, and the risk was particularly high in elderly patients. The occurrence of SIBO-related symptoms was significant in long-term use of PPIs and in patients with positive GBT.

Herbal medicine could be an option for atopic dermatitis (AD) treatment for those suffering from global public health. HMB is a new combination of three herb extracts, consisting of the Ha-Rak (HR) remedy extract, Piper betle (PB) extract, and Garcinia mangostana (GM) extract in equal proportions, using Thai traditional medicine theory, that uses a combination of medications that can improve therapeutic efficacy and reduce side effects and toxicity. HMB extract has anti-inflammatory and antiallergic properties, is a component for AD treatment, and tends to develop topical products. Drug registration requires stability data. Results from drug stability testing affect not only the efficacy of the drug but also its safety. The aim of this study was to investigate stability through forced degradation and an accelerated study of extracts. Chemical content analysis and in vitro biological activities such as anti-inflammatory and antiallergic activities determined the effects of all examined samples. Anti-inflammatory and antiallergic effects were assessed by inhibiting nitric oxide synthesis in RAW 264.7 cells and β-hexosaminidase release in RBL-2H3 cells, respectively. High-performance liquid chromatography (HPLC) assessed content indicators. Moisture and temperature hydrolysis had no significant differences in the chemical or biological properties of the HMB. However, the HMB demonstrated sensitivity to alkaline hydrolysis, showed low anti-inflammatory activity, and decreased hydroxychavicol, eugenol, and α-mangostin contents. The contents of the three compounds also decrease with acid hydrolysis. For the accelerated study, anti-inflammatory and antiallergic effects and hydroxychavicol amount were not significantly different after 180 days at 40°C and 75% RH. Therefore, the contents of eugenol and α-mangostin were changed. Eugenol in HMB decreased significantly from the 15^th day until the 180^th day of storage. In addition, α-mangostin amounts in HMB decreased slightly on 180^th day. Fortunately, reducing the two chemicals did not affect anti-inflammatory or antiallergic effects. For stability, combination extract should be stored in a closed container in the refrigerator at a low temperature and protected from light, high temperature, oxygen, and pH. Further HMB development should avoid pH or oxidation processes or components.

Wound healing comprises an intricate process to repair damaged tissue. Research on plant extracts with properties to expedite wound healing has been of interest, particularly their ability to enhance the stemness of keratinocyte stem cells. Hence, the present study aims to determine the wound healing and stemness potentiation properties of an ethanolic extract derived from Cucurbita moschata fruit pulp (PKE). Human keratinocytes (HaCaT) and primary skin fibroblast cells were used in this study. The migration of the cells was examined by using a scratch wound healing assay, and spheroid behavior was determined by using a spheroid formation assay. The proteins related to migration and stemness were further measured by using Western blotting to explore the mechanism of action of PKE. The methods used to evaluate PKE's antioxidant properties were 2,2-diphenyl-2-picrylhydrazyl (DPPH) scavenging, ABTS radical scavenging activity, and superoxide anion radical scavenging (SOSA) assays. The phytochemistry of the PKE was investigated using phytochemical screening and high-performance liquid chromatography (HPLC) analysis. The results of this study indicate that nontoxic concentrations of PKE increase the rate of migration and spheroid formation. Mechanistically, PKE increased the expression of the migratory-related protein active FAK (phosphorylated FAK), and the subsequence increased the level of p-AKT. The expression of stem cell marker CD133, upstream protein signaling β-catenin, and self-renewal transcription factor Nanog was increased. The PKE also possessed scavenging properties against DPPH, ABTS, and SOSA. The phytochemistry analyses exhibited the presence of alkaloids, glycosides, xanthones, triterpenes, and steroids. Additionally, bioactive compounds such as ɑ-tocopherol, riboflavin, protocatechuic acid, β-carotene, and luteolin were detected. The presence of these chemicals in PKE may contribute to its antioxidant, stem cell potentiation, and wound-healing effects. The findings could be beneficial in the identification of valuable natural resources that possess the capacity to be used in the process of wound healing through the potentiation of stemness via a readily detectable molecular mechanism.