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Combined Inositol Hexakisphosphate and Inositol Supplement Consumption Improves Serum Alpha-Amylase Activity and Hematological Parameters in Streptozotocin-Induced Type 2 Diabetic Rats
This study evaluated the effect of combined inositol hexakisphosphate (IP6) and inositol supplement on organ weight, intestinal ATPase activities, complete blood count, and serum analytes in streptozotocin (STZ)-induced type 2 diabetic rats. High-fat diet and a single intraperitoneal injection of streptozotocin (35 mg/kg body weight) were used to induce type 2 diabetes mellitus in Sprague–Dawley rats. The diabetic groups were then treated with either combined IP6 and inositol supplement or glibenclamide for four weeks. Organ weights, intestinal ATPase activities, complete blood count, serum α-amylase, total protein, albumin, and globulin content were determined. Pancreatic weight was significantly reduced while relative kidney and liver weights were elevated in the group treated with combined IP6 and inositol supplement compared to the nondiabetic control. Serum α-amylase activity for the glibenclamide and combination treated groups was significantly improved compared to that of the untreated diabetic group. Red cell distribution width percentage was significantly lower in the combination treated group compared to that in the untreated diabetic group, while intestinal ATPase activities were unaffected by the treatment regime. Combined IP6 and inositol supplement consumption may protect people with diabetes from increased risk of cardiovascular diseases due to the supplement's ability to maintain red cell distribution width percentage towards the normal control group.
Protective Effects of Aqueous Extract of Baillonella toxisperma Stem Bark on Dexamethasone-Induced Insulin Resistance in Rats
The aim of this study was to evaluate the effects of the aqueous extract of Baillonella toxisperma stem bark on dexamethasone-induced insulin resistance in rats. A quantitative phytochemical study was done on the aqueous extract of Baillonella toxisperma for the total phenol, flavonoid, and flavonol determination. Insulin resistance was induced by intraperitoneal injection of dexamethasone (1 mg/kg) for 8 days, one hour before oral administration of different treatments (extract at doses of 60, 120, and 240 mg/kg and metformin at 40 mg/kg). During the test, body weight and blood glucose level were evaluated on days 1 and 8. At the last day of treatment, the glucose tolerance test was performed in rats; after that, blood samples were collected for triglycerides, total cholesterol, LDL and HDL cholesterols, transaminases (ALT and AST), and total protein level determination. Organs (heart, liver, pancreas, and kidneys) were also collected for the relative organ weight determination. The results showed that the aqueous extract of B. toxisperma is rich in total phenols, flavonoids, and flavonols. This extract significantly reversed the metabolic alterations (lipid profile, protein level, and transaminase activity) induced by dexamethasone in rats. At doses of 120 and 60 mg/kg, Baillonella toxisperma also significantly decreases (; ) postprandial hyperglycemia in insulin resistance rats. The results suggest that Baillonella toxisperma can manage insulin resistance and may be useful for the treatment of type 2 diabetes mellitus.
Effect of Calcium and Vitamin D Supplements as an Adjuvant Therapy to Metformin on Menstrual Cycle Abnormalities, Hormonal Profile, and IGF-1 System in Polycystic Ovary Syndrome Patients: A Randomized, Placebo-Controlled Clinical Trial
Objective. This study aims to investigate the effect of combining calcium and vitamin D supplements with metformin on menstrual cycle abnormalities, gonadotropins, and IGF-1 system in vitamin D-deficient/insufficient PCOS women. Study Design. This is a randomized, placebo-controlled clinical trial. Setting. This study was performed in Damascus University of Obstetrics and Gynecology Hospital and Orient Hospital, in Damascus, Syria. Materials and Methods. Forty PCOS women with 25-OH-vitamin D < 30 ng/ml were randomly assigned to take either metformin (1500 mg/daily) plus placebo or metformin (1500 mg/daily) plus calcium (1000 mg/daily) and vitamin D3 (6000 IU/daily) orally for 8 weeks. Serum levels of gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-1 (IGFBP-1) were detected at the baseline during the early follicular phase of a spontaneous or induced menstrual cycle and after 8 weeks of intervention (except for the final gonadotropins levels which were assayed from samples obtained during the early follicular phase of a spontaneous menstrual cycle). Results. Thirty-four patients (85%) completed the study. After 8 weeks of intervention, calcium and vitamin D co-supplementation led to a significant increase in 25-OH-vitamin D levels and calcium levels in the supplementation group compared to the other group (change in 25-OH-vitamin D levels: +19.38 ± 7.78 vs +0.11 ± 4.79 ng/ml, respectively; ) (change in calcium levels: +0.83 ± 0.82 vs +0.01 ± 0.86 mg/dl, respectively; ). An improvement in menstrual cycle irregularity was detected in 38.5% and 58.8% of patients in metformin-placebo group and metformin-calcium-vitamin D group, respectively; but the change was statistically significant only in the supplementation group (). Nevertheless, the means of changes from baseline in gonadotropins levels (serum levels of LH, FSH, and LH to FSH ratio) and the studied parameters of IGF-1 system (serum levels of IGF-1, IGFBP-1, and IGF-1 to IGFBP-I ratio) did not differ significantly between the two groups. Conclusions. Calcium and vitamin D supplements can support metformin effect on regulation of menstrual cycle irregularity in vitamin D-deficient/insufficient PCOS patients, but this effect is not associated with any significant changes in gonadotropins or IGF-1 system. These results suggest a possible role of calcium and vitamin D supplements in managing PCOS. However, further studies are needed to identify the underlying mechanisms. The Clinical Trial Registration Number is NCT03792984.
Evaluation of Anti-HIV-1 Integrase and Anti-Inflammatory Activities of Compounds from Betula alnoides Buch-Ham
Betula alnoides is a medicinal plant in Thai traditional longevity preparations. The crude extracts of this plant possess various biological activities. However, the isolated compounds from this plant have no reports of anti-HIV-1 integrase (IN) activity. Therefore, the present study aims to investigate the anti-HIV-1 integrase and anti-inflammatory effects of isolated compounds from this plant and predict the interaction of compounds with integrase active sites. From the bioassay-guided fractionation of the ethanol extract of B. alnoides stems using chromatographic techniques, five pentacyclic triterpenoid compounds were obtained. They are betulinic acid (1), betulin (2), lupeol (3), oleanolic acid (4), and ursolic acid (5). Compound 2 exhibited the most potent inhibitory activity against HIV-1 IN, with an IC50 value of 17.7 μM. Potential interactions of compounds with IN active sites were investigated using computational docking. The results indicated that active compounds interacted with Asp64, a residue participating in 3′-processing, and Thr66, His67, and Lys159, residues participating in strand-transfer reactions of the integration process. Regarding anti-inflammatory activity, all compounds exerted significant inhibitory effects on LPS-induced nitric oxide production (IC50 < 68.7 μM). Thus, this research provides additional scientific support for the use of B. alnoides in traditional medicine for the treatment of HIV patients.
Synthesis of an Activatable Tetra-Substituted Nickel Phthalocyanines-4(3H)-quinazolinone Conjugate and Its Antibacterial Activity
The aim of this study was to synthesize a series of nickel(II)phthalocyanines (NiPcs) bearing four 4(3H)-quinazolinone ring system units, (qz)4NiPcs 4a–d. The electronic factors in the 4(3H)-quinazolinone moiety that attached to the NiPc skeleton had a magnificent effect on the antibacterial activity of the newly synthesized (qz)4NiPcs 4a–d against Escherichia coli. The minimum MICs and MBCs value were recorded for compounds 4a, 4b, 4c, and 4d, respectively. The results indicated that the studied (qz)4NiPcs 4a–d units possessed a broad spectrum of activity against Escherichia coli. Their antibacterial activities were found in the order of 4d > 4c > 4b > 4a against Escherichia coli, and the strongest antibacterial activity was achieved with compound 4d.
GRP78/BIP/HSPA5 as a Therapeutic Target in Models of Parkinson’s Disease: A Mini Review
Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by selective loss of dopamine neurons in the substantia nigra pars compacta of the midbrain. Reports from postmortem studies in the human PD brain, and experimental PD models reveal that endoplasmic reticulum (ER) stress is implicated in the pathogenesis of PD. In times of stress, the unfolded or misfolded proteins overload the folding capacity of the ER to induce a condition generally known as ER stress. During ER stress, cells activate the unfolded protein response (UPR) to handle increasing amounts of abnormal proteins, and recent evidence has demonstrated the activation of the ER chaperone GRP78/BiP (78 kDa glucose-regulated protein/binding immunoglobulin protein), which is important for proper folding of newly synthesized and partly folded proteins to maintain protein homeostasis. Although the activation of this protein is essential for the initiation of the UPR in PD, there are inconsistent reports on its expression in various PD models. Consequently, this review article aims to summarize current knowledge on neuroprotective agents targeting the expression of GRP78/BiP in the regulation of ER stress in experimental PD models.