Research in Pharmaceutical Sciences最新文献

Background and purpose: Osteoarthritis (OA) is a common joint disease that affects millions of people worldwide and is characterized by cartilage degeneration, stiffness, and limited mobility. This clinical trial aimed to investigate the efficacy and safety of a herbal combination of Colchicum autumnale root, Withania somnifera root, and Pistacia lentiscus gum in the relief of knee OA symptoms.

Experimental approach: Seventy patients diagnosed with knee OA were randomized to receive the herbal product or a placebo for 6 weeks. Pain and functional outcomes were measured using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and Visual Analogue Scale (VAS). The heel-to-thigh distance parameter was also assessed by measuring the distance between the thigh and heel at maximum knee flexion in the prone position.

Findings/results: Significant improvements were observed in WOMAC scores for pain, stiffness, and physical function in the herbal product group compared to placebo at 3 and 6 weeks. VAS scores confirmed these results and showed lower pain intensity in the herbal product group. Heel-to-thigh distance decreased significantly within all groups during the study.

Conclusion and implications: This study provided evidence for the efficacy of the herbal combination in the management of knee OA symptoms and was well tolerated by all patients with no severe adverse effects. The observed benefits emphasized the potential of herbal medicines as a complementary approach in the management of knee OA. Further research is needed to fully elucidate the therapeutic mechanisms and optimize the clinical application of this herbal combination.

Background and purpose: Menopause can increase the risk of cardiovascular diseases, diabetes mellitus, and metabolic syndrome, principally due to estrogen deficiency. In the current experiment, protective effects of selective estrogen receptor modulators (SERMs) and estradiol (E2), alone and combined, were evaluated in a rat model of menopause.

Experimental approach: Forty-eight female Wistar rats underwent ovariectomy to induce a menopause model. Then, the animals were subjected to receive SERMs including tamoxifen (TAM), raloxifene (RAL), and bazedoxifene (BZA) and E2. Finally, serum and liver tissue samples were collected post-treatment for experimental analysis.

Findings/results: The induction of menopause by ovariectomy reduced the body weight of animals and altered their food intake. TAM, RAL, ethinyl E2 (EE2), and BZA/conjugated estrogens (BZA/CE) improved the ovariectomy-induced elevation of total cholesterol and low-density lipoprotein (LDL) cholesterol significantly. In this regard, the lowering effects of SERMs were significantly greater than EE2. The increased levels of triglycerides were also alleviated by RAL, EE2, and BZA/CE but not TAM. Moreover, the combination of SERMs, especially BZA/CE therapy, had significantly increasing effects on high-density lipoprotein (HDL) cholesterol levels, in a more effective manner than E2 therapy alone. Low-density lipoprotein receptor gene and protein expression levels were also significantly increased by SERMs. The HDL2 subfraction was found to be significantly enhanced in TAM, RAL, and BZA/CE therapy.

Conclusion and implications: The therapy with SERMs, alone or in combination with E2, may be efficiently utilized instead of E2 replacement therapy in post-menopausal conditions.

Background and purpose: Canna edulis (C. edulis) and Maranta arundinacea (M. arundinacea) are potential medicinal plants. This study investigated the preventive effect of dietary fibers from C. edulis and M. arundinacea rhizomes against metabolic diseases and gut dysbiosis promoted by a high-fat diet (HFD).

Experimental approach: Twenty-four male mice were divided into 4 groups and fed a low-fat diet, HFD, or HFD combined with 10% C. edulis fiber or M. arundinacea fiber for 12 weeks. Subsequently, the indicators of metabolic syndromes and gut microbiota composition were investigated.

Findings/results: C. edulis fiber effectively prevented obesity and counteracted HFD-induced dyslipidemia. C. edulis and M. arundinacea fibers prevented type 2 diabetes, but C. edulis fiber was more effective in regulating glucose tolerance and insulin than M. arundinacea. C. edulis fiber also reduced steatosis and inflammation in the liver. 16S rRNA sequencing of fecal microbiota revealed that the fibers decreased the abundance of Desulfobacterota, but only C. edulis increased Bacteroidota while decreasing Firmicutes. C. edulis fiber elevated the abundance of beneficial microbiota, including Lactobacilus reuteri, L. johnsonii, and Bacteroides fragilis, while lowering the pathogenic species Mucispirillum sp. Otherwise, M. arundinacea fiber increased the beneficial species L. murinus and Faecalibacterium prausnitzii, and pathogenic species Mucispirillum sp.

Conclusion and implications: C. edulis and M. arundinacea fibers exerted ameliorative effects against metabolic diseases and gut dysbiosis caused by HFD. However, C. edulis fiber was more effective than M. arundinacea. Therefore, C. edulis fiber could be a candidate for supplements preventing metabolic diseases and gut dysbiosis.

Background and purpose: Colitis is a type of inflammatory bowel disease (IBD) with an unknown and complex etiology. Lacosamide is a known antiepileptic drug for which anti-inflammatory effects have been reported. This study investigates the ameliorative effects of lacosamide on acetic acid-induced colitis in rats.

Experimental approach: Male Wistar rats were divided into different interventional groups, including normal and control colitis groups (normal saline, 5 mL/kg), two colitis groups (dexamethasone, 1 mg/kg) and mesalazine (100 mg/kg), four colitis groups received oral lacosamide (10, 20, or 40 mg/kg), or lacosamide enema (10 mg/kg). The treatments were conducted for five days following disease induction by acetic acid (3.5%, 2 mL). Colitis indices in tissue samples, as well as biochemical factors such as myeloperoxidase (MPO), malondialdehyde (MDA), and ferric reducing antioxidant power (FRAP), were assessed.

Findings/results: The trend of body weight drop was stopped by using lacosamide. Colon weight as well as ulcer index significantly decreased in the groups that received lacosamide (10-40 mg/kg via oral or rectal) compared to the control group. Histological findings showed that lacosamide (10 and 20 mg/kg via oral and enema) reduced inflammation markers and tissue damage while causing tissue regeneration. Levels of MDA and MPO significantly decreased while FRAP increased in lacosamide (10 and 20 mg/kg) groups, both oral and via enema.

Conclusion and implications: Findings highlight the potential of lacosamide as an effective treatment in reducing inflammation and promoting ulcer healing. However, further studies are needed to elucidate the precise mechanisms of lacosamide's anti-inflammatory effects and to confirm these results in human disease.

Background and purpose: Breast cancer is one of the leading causes of death among women worldwide, with rising incidence rates, particularly in rapidly developing countries such as Iran. This study aimed to investigate the relationship between lipid metabolism enzymes, fatty acid synthase (FASN), ATP-citrate lyase (ACLY), and acyl-CoA synthetase long-chain family member 4 (ACSL4), and patient survival, with a focus on their potential role in breast cancer metastasis. In addition, we evaluated the prognostic significance of human epidermal growth factor receptor 2 (HER-2) overexpression in breast cancer patients.

Experimental approach: A total of 52 breast cancer tissue samples were collected from patients at Ordibehesht Clinic in Isfahan, Iran. RNA was extracted and analyzed using qRT-PCR to quantify the expression of FASN, ACLY, and ACSL4. Kaplan-Meier survival curves and log-rank tests were applied to assess survival rates and metastasis.

Findings/results: The Kaplan-Meier analysis showed an average time to metastasis of 36.18 months. No significant associations were found between metastasis and the expression levels of ACLY, FASN, or ACSL4. In contrast, HER-2 expression was significantly associated with metastasis, underscoring its potential as a critical prognostic marker. Other clinicopathological factors, including tumor grade, stage, size, and receptor status, were not significantly related to metastasis.

Conclusion and implications: Our study highlights the importance of HER-2 as a key prognostic marker in breast cancer and suggests that further research is required to clarify the mechanisms underlying its role in cancer progression.

Background and purpose: Radiotherapy is an essential treatment for breast cancer, but radioresistance remains a major obstacle. Studies suggest that statins and cyclooxygenase-2 (COX-2) inhibitors can enhance radiotherapy, yet few have examined their combined effects on breast cancer radiosensitivity. This study investigates the impact of meloxicam and rosuvastatin pretreatment on the radiosensitivity of MCF-7, T-47D, and MDA-MB-231 breast cancer cell lines.

Experimental approach: MCF-7, T-47D, and MDA-MB-231 cells were pretreated with varying concentrations of meloxicam, rosuvastatin, or both. Their response to radiation was evaluated using micronucleus, clonogenic, catalase, and superoxide dismutase (SOD) assays to assess chromosomal damage, cell survival, oxidative stress (via hydrogen peroxide degradation), and SOD antioxidant enzyme activity, respectively.

Findings/results: Pretreatment with combined rosuvastatin (R) and meloxicam (M) at R2+M10 μM, R10+M50 μM, and R20+M100 μM increased genotoxicity and reduced colony formation across all irradiated cell lines compared to radiation alone. R10 μM, R10+M50 μM, and R20+M100 μM decreased catalase activity across irradiated cell lines compared to radiation alone, whereas R2+M10 μM decreased catalase activity significantly only in T-47D cells. Pretreatment with R10 μM, R2+M10 μM, R10+M50 μM, and R20+M100 μM reduced SOD activity in all irradiated cell lines compared to radiation alone.

Conclusion and implications: The combination of rosuvastatin and meloxicam at specific concentrations increased the radiation sensitivity of MCF-7, T-47D, and MDA-MB-231 cells. Combined pretreatment with rosuvastatin 10 μM and meloxicam 50 μM notably enhanced genotoxicity while reducing colony formation, catalase activity, and SOD activity compared to radiotherapy alone in MCF-7, T-47D, and MDA-MB-231 cell lines.

Background and purpose: In traditional medicine, species of Cleome (known in Persian as alaf-e-mar) are used to treat wounds and earaches, as well as for their antihelmintic, carminative, and anti-arthritic properties. Flavonoids, among the most significant phytochemicals in this family, hold pharmacological importance, mainly due to their ability to scavenge free radicals.

Experimental approach: Cleome turkmena Bobrov was collected and extracted in methanol. Compounds were isolated by open-column and size-exclusion chromatography. Free radical scavenging ability and reduction potential of isolated flavonols along with allantoin were determined according to the scavenging of the DPPH (diphenyl-picrylhydrazyl) radical and reducing power of Fe³+ assays. A theoretical study of their antioxidant capacity was done using density functional theory calculations.

Findings/results: Allantoin (compound 1), 2 known flavonol glycosides (compounds 2, 4), and 1 undescribed flavonol glycoside (compound 3) were isolated, and their structures were identified using different spectroscopic techniques for the first time in this plant. Among them, compound 4, quercitin-3-O-β-D-glucoside-7-O-α-L-rhamnoside, exhibited the best free radical scavenging and reducing power effects compared to the standards.

Conclusion and implications: All flavone glycosides isolated from Cleome turkmena Bobrov showed favorable DPPH radical scavenging and Fe³+ reducing power.

Background and purpose: Heart disease is a major global health problem. Gallic acid (GA) possesses cardioprotective properties. This study aimed to evaluate the therapeutic effects of GA pretreatment in ischemia-reperfusion (I/R) and elucidate its underlying mechanisms.

Experimental approach: Forty adult male Wistar rats were subjected to this experiment. GA was given to the rats through gavage at doses of 15 and 30 mg/kg/day, 10 days before the induction of ischemia. To induce I/R, the left anterior descending coronary artery was occluded for 30 min, and reperfusion continued for 24 h. Malondialdehyde (MDA) levels, antioxidant enzyme activity, and inflammatory cytokines were assessed using kits. Myocardial injury markers were analyzed by ELISA, and infarct size was assessed through 2,3,5-triphenyltetrazolium chloride staining. Real-time polymerase chain reaction was utilized to quantify the relative gene expression of Bax and Bcl-2.

Findings/results: The findings indicated that pretreatment with GA led to significant improvement in inflammatory cytokines, antioxidant enzyme activity, and a decrease in MDA levels. GA also decreased infarct size and myocardial injury markers significantly. Moreover, pretreatment with GA revealed a significant increase in the expression of the Bcl-2 gene, while the expression of the Bax gene decreased.

Conclusion and implications: Inclusively, the results suggested that GA may hold significant potential as a therapeutic agent for reducing myocardial injury in the context of I/R, with 30 mg/kg/day proving more effective than 15 mg/kg/day, offering a promising path for further investigation.

Background and purpose: The estrogen receptor alpha-36 (ER-α36) is an alternative splice variant of classical ER-α66 and is abundantly present in both ER-α66-positive and ER-α66-negative breast tumor cells. Given its clinical relevance, developing targeted strategies against this isoform is of particular significance to breast cancer research. This study aimed to develop an ER-α36-specific recombinant biosimilar single-chain variable fragment (scFv) antibody.

Experimental approach: The primary amino acid sequence of the anti-ER-α36 scFv was retrieved from patent US20110311517A1. An expression cassette harboring the scFv coding sequence was designed and incorporated into the backbone of the pET-28a(+) expression vector for recombinant expression in Escherichia coli (E. coli) BL21(DE3) cells. Expression conditions were then optimized, and the protein was purified using immobilized metal affinity chromatography. The binding of the purified scFv to ER-α36-expressing breast cancer cells was assessed using enzyme-linked immunosorbent assay (ELISA) and flow cytometry.

Findings/results: Characterization using sodium dodecyl sulfate polyacrylamide gel electrophoresis and western blotting experiments revealed a molecular weight of 29 kDa for the expressed scFv antibody. Relative quantification revealed the highest scFv protein expression level 16 h after induction with 1 mM isopropyl β-D-1-thiogalactopyranoside at 25 °C. Flow cytometry and ELISA assays demonstrated specific binding of the scFv to ER-α36 protein on MDA-MB-231 breast cancer cells, while no interaction was detected with ER-α36-negative MCF-10A normal mammary epithelial cell line.

Conclusion/implications: The anti-ER-α36 scFv antibody fragment was successfully expressed using the E. coli expression system, and the purified protein was able to specifically recognize and bind to ER-α36-expressing human breast cancer cells.

Background and purpose: This study explored the impact of the hydroalcoholic extract of Medusomyces gisevii L. (HEMG), a promising source for dietary use, on NAFLD in male mice.

Experimental approach: The essential oil of MG was characterized using GC-MS and the HEMG, obtained through continuous maceration. Male albino mice were subjected to 7 groups (n = 9), including normal diet, high-fat diet (HFD, 12 weeks), HEMG (62.5, 125, 250, and 500 mg/kg, orally, 8 weeks), or vitamin E (20 mg/kg, orally, 8 weeks) supplementation with HFD. Blood samples were analyzed for serum biomarkers, and liver mitochondria were isolated to assess oxidative stress markers. Histopathological examinations of liver tissue were conducted.

Findings/results: MG was rich in cyclohexanol, carvacrol, and phenol, with HEMG exhibiting an antioxidant activity of 50.14 ± 3.56 μg/mL. It contained 73.47 ± 0.85 mg of gallic acid equivalents per g of TPC and 62.56 ± 1.30 mg/g of TTC, indicating the significant antioxidant properties of HEMG. Mice on an HFD exhibited elevated serum biomarkers, including ALT, AST, ALP, TG, TC, and LDL, along with a reduction in HDL levels. Oxidative stress factors, including ROS, protein carbonyl, and MDA, increased, while mitochondrial function, GSH, catalase, and SOD were decreased in the NAFLD groups. Furthermore, treatment with HEMG supplementation led to improvements in serum biomarkers and enhanced oxidative stress markers, thus alleviating liver damage and hepatic steatosis caused by the HFD.

Conclusion and implications: These results suggest that HEMG holds promise as a candidate in addressing NAFLD.