Portulaca oleracea L seed extracts counteract diabetic nephropathy through SDF-1/IL10/PPARγ-mediated tuning of keap1/Nrf2 and NF-κB transcription in Sprague Dawley rats.

BACKGROUND & OBJECTIVE: While oxidative stress is the key player driving diabetic nephropathy (DN), firm glycemic control remains the pillar prophylactic measure. Purslane was extensively described as a potent hypoglycemic and hypolipidemic agent owing to its rich content of antioxidants. Therefore, this report aimed to assess the renoprotective potentials of methanol (MO) and methylene chloride (MC) fixed oil extracts of purslane seeds in a diabetic nephropathy (DN) model. METHODS: Purslane seeds were extracted using absolute methanol and methylene chloride, and type-1 diabetes was induced with a single 55 mg/kg dose of Streptozotocin (STZ) dissolved in 100 mmol/L citrate buffer (pH 4.5), and then diabetic animals were received MO, MC, for 42 consecutive days to compare their antidiabetic effect relative to the reference drug "Losartan". Renal functions and DN biomarkers were weekly assessed, and the relative expression of different oxido-inflammatory mediators was quantified in diabetic kidneys by RT-PCR. Data were statistically analyzed using GraphPad Prism 9.0.2. RESULTS: The oral administration of MO and MC extracts (250 mg/kg/day) significantly ameliorated the body weight loss (P < 0.0001 / each), fasting blood glucose levels (FBG) (P < 0.0001 / each), urine volume (P < 0.0001 / each), as well as serum creatinine (P < 0.0001 / each), uric acid (P = 0.0022, 0.0052), and blood urea nitrogen (BUN) (P = 0.0265, 0.0338); respectively, compared with the untreated diabetic rats. In addition, both extracts restored the effectuality of antioxidative machinery in diabetic kidneys as indicated by a significant reduction of ROS accumulation and lipid peroxidation; higher GSH content, and promoted activity of glutathione reductase and superoxide dismutase antioxidant enzymes (P < 0.0001 / each). Histologically, both extracts alleviated the DN-structural alterations including the glomerular congestion and tubular degeneration, with MC-treated kidneys showing near to normal architecture. The transcription profiles of all treated kidneys revealed a significantly downregulated expression of TNF-α, IL-6, Keap1 and NF-κB genes, concomitant with a significant upregulation of SDF-1, IL-10, Nrf2, HO-1, and PPARγ gene expression (P < 0.0001 / all). CONCLUSION: These findings highlight the remarkable DN-prophylactic potentials of purslane extracts mediated by neutralizing the hyperglycemia-induced ROS accumulation, and circumventing the downstream inflammatory cascades, surpassing the reference angiotensin receptor blocker; i.e. Losartan.

Toxicological profiling of a de novo synthesized benzimidazole derivative with potent and selective proapoptotic potentials against breast cancer.

This study aimed to investigate the toxicological profile of 1-(6-(1H-benzo[d]imidazole-2-yl)-2-methylpyridin-3-yl) ethanone (BMPE), both in vitro and in vivo. The proapoptotic/necrotic and cell cycle arrest potentials of BMPE were assessed in MCF-7 cell line. The in vivo toxicology was assessed in female Balb/c mice by repeated dosing of 5, 25, and 50 mg/kg for 21 consecutive days, then different biochemical, inflammatory, and oxidative markers were assessed in sera/tissue homogenates of treated animals. The new derivative showed a potent selective cytotoxicity against malignant cell lines with IC50 value 0.2 µM/mL, while the cytotoxic effect on normal Wi-38 cells was observed at IC50 value 0.4 µM/mL; i.e. twofold the effective anticancer dose. BMPE exhibited an early DNA fragmentation-derived cell apoptosis observed at the G0/G1 checkpoint. In vivo, BMPE was biochemically/immunologically tolerable at a pharmacological dose range of 5-25 mg/kg, with no significant rates of mortality/morbidity and minimal-to-moderate histopathological alterations recorded. The new derivative represents an attractive therapeutic candidate for breast cancer, considering its noticeable modulatory effect on the oxidative-inflammatory axis that would relate to its potent antitumor effect.

Urinary transferrin and proinflammatory markers predict the earliest diabetic nephropathy onset.

AIM: This study aimed to determine the earliest markers of diabetic nephropathy (DN) onset with discriminative potentials from controlled diabetes (CD). METHODS: Sixty male Wistar rats were allocated into three groups (20/group), the two diabetic groups CD and DN received 45 and 65 mg/kg STZ in 0.1 mole/L citrate buffer, respectively, while the control group received only the vehicle. Serum/urinary levels of glomerular, tubular, oxidative and proinflammatory markers were weekly monitored. RESULTS: Each diabetic group showed a different pattern of inflammatory, oxidative and signs of nephropathy along the study period, but none had a discriminative power until the fourth week. At this time point, levels of urinary transferrin, serum/urinary IL-6 and TNF-α as well as urinary IL-18 were significantly higher in DN group compared to CD (p = 0.0217, <0.0001, 0.0005, 0.0004, 0.0006, 0.0019, respectively). Predictive thresholds of these markers were calculated by receiver operating characteristic (ROC) curve that showed area under curve (AUC) of 0.9375 for transferrin with cut-off value of 35.2 mg/dL and 1.000 for serum/urinary IL-6 and TNF-α and urinary IL-18 with cut-of values 224.1, 82.11, 6.596, 125.9 and 21.86 pg/mL, respectively. CONCLUSION: Urinary transferrin and the inflammatory endpoints proposed in this study might represent promising biomarkers for the early DN onset.

Pulicaria crispa mitigates nephrotoxicity induced by carbon tetrachloride in rats via regulation oxidative, inflammatory, tubular and glomerular indices.

CONTEXT: Carbon tetrachloride (CCl4) induces oxidative stress in various tissues by altering antioxidants defense system. Recently, there has been a substantial use of phytotherapy to treat different diseases. OBJECTIVE: This study was designed to evaluate the curative effect of Pulicaria crispa (Forssk.) Benth et Hook (Family Asteraceae) aerial parts ethanol extract against CCl4 induced toxicity in rats kidneys. MATERIALS AND METHODS: Nephrotoxicity was induced by intraperitoneal injection with CCl4 in a dose of 0.5 mL/kg b.wt./twice a week for six consecutive weeks. Serum kidney function tests, oxidative stress markers, inflammatory cytokines, nephrotoxicity biomarkers and histopathological observation were evaluated. RESULTS: CCl4 increased serum kidney function parameters, malondialdehyde level, inflammatory cytokines, and nephrotoxicity markers, while decreased certain oxidative stress indices as superoxide dismutase and glutathione refereeing to the control group (p < 0.0001). Administration of P. crispa ethanol extract to CCl4 injured rats attenuated these changes with variable degrees. The results were confirmed through the observed amelioration of the renal histological architectures. CONCLUSION: P. crispa ethanol extract possesses potent curative effect against CCl4-induced nephropathy through improvement of kidney function, oxidative stress, inflammatory and nephrotoxicity index and the renal histopathological features. To establish the therapeutic and pharmacological applications of the plant, additional researches are required.

Bioactive compounds and therapeutic role of Brassica oleracea L. seeds in rheumatoid arthritis rats via regulating inflammatory signalling pathways and antagonizing interleukin-1 receptor action.

CONTEXT: Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease characterized by aggressive and systematic polyarthritis. OBJECTIVE: The present study aimed to isolate and identify the phenolic constituents in Brassica oleracea L. (Brassicaceae) seeds methanolic extract and evaluates its effect against rheumatoid arthritis in rats referring to the new therapy; interleukin-1 receptor antagonist (IL-1RA). MATERIALS AND METHODS: The GC/MS profiling of the plant was determined. Arthritis induction was done using complete Freund's adjuvant. Arthritis severity was assessed by percentage of edema and arthritis index. IL-1 receptor type I gene expression, interleukin-1ß (IL-1ß), oxidative stress markers, protein content, inflammatory mediators, prostaglandin-E2 (PGE2), genetic abnormalities and the histopathological features of ankle joint were evaluated. RESULTS: For the first time twelve phenolic compounds had been isolated from the seeds extract. Treatment with extract and IL-1RA improved the tested parameters by variable degrees. CONCLUSIONS: RA is an irreversible disease, where its severity increases with the time of induction. Brassica oleracea L. seeds extract is considered as a promising anti-arthritis agent. IL-1 RA may be considered as an unusual therapeutic agent for RA disease. More studies are needed to consider the seeds extract as a nutraceutical agent and to recommend IL-1RA as a new RA drug.

Downregulation of fibrosis and inflammatory signalling pathways in rats liver via Pulicaria crispa aerial parts ethanol extract.

CONTEXT: Liver is a vital organ for the detoxification of toxic substances in the body, where fibrosis is the major cause of liver damage. Pulicaria crispa processes many therapeutic applications such as antioxidant, antimicrobial, anticancer and anti-ulcerative agent. OBJECTIVE: This study aimed to modulate the fibrosis and inflammatory signalling pathways in carbon tetrachloride (CCl4)-induced liver damage in rats via treatment with Pulicaria crispa aerial parts ethanol extract (PCEE). MATERIALS AND METHODS: CCl4 was intraperitoneally injected at a dose of 0.5 mL/kg b.wt./twice a week/six consecutive weeks, PCEE was orally allocated at a dose of 250 mg/kg b.wt./day/six weeks and silymarin was orally administrated at a dose of 100 mg/kg, b.wt/day/six weeks. The plant extract evaluation was done through measuring aspartate and alanine aminotransferases (AST& ALT), alkaline phosphatase (ALP), total lipids (TP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low level glycoprotein-cholesterol (LDL-C), alpha fetoprotein (AFP), reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), tumour necrosis factor-α (TNF-α) and interleukin 6 (IL-6). The liver architectures were also estimated. RESULT: The phytochemical analysis of the extract showed the presence of sterols and/or triterpenoids. Treatments with plant extract suppressed significantly (p < 0.0001) the levels of AST, ALT, ALP, TP, TG, TC, LDH-C, MDA, NO, AFP, TNF-α and IL-6, while increased (p < 0.0001) the levels of HDL-C, GSH and SOD. The histopathological features confirmed the therapeutic role of the plant extract. CONCLUSION: PCEE succeeded to exert anti-fibrotic, anti-inflammatory and anti- oxidants effects in CCl4-induced liver fibrosis.

Isolation and characterization of flavonoid compounds from Stachytarpheta jamaicensis (L.) Vahl and its role as anti-gastro ulcerative agent in rats.

CONTEXT: Stomach ulcer is one of the most common gastrointestinal problems in the world. OBJECTIVE: This study aimed to isolate flavonoid compounds from methanol extract of the aerial parts of Stachytarpheta jamaicensis (L.) Vahl. and evaluate its protective and therapeutic effects against gastric ulcer. MATERIALS AND METHODS: Chromatographic techniques were used for the identification of the isolated compounds. To explore the effects of the plant extract, it was administrated by oral gavage for one week either before or post-ethanol ulcer induction. Ranitidine was also evaluated as a reference drug. Stomach pH, gastric juice volume, lesions number, glutathione, superoxide dismutase, malondialdehyde, succinate dehydrogenase, lactate dehydrogenase, acid phosphatase, Interleukin-10, intracellular adhesion molecule-1, prostaglandin E2, and total protein levels were estimated in gastric tissue. Stomach histopathological features were also monitored. RESULTS: Six flavonoid compounds were isolated, where five of them were isolated for the first time (vitexin, isovitexin, apigenin 7,4'-dimethyl ether, 5,7,2'-trimethoxyflavone, and scutellarein), while apigenin was previously reported. Treatment with plant extract recorded amelioration in all the biochemical parameters. CONCLUSION: The methanol extract of plant aerial parts had prophylactic and treatment effects against gastric ulcer in rats, where its treatment effect exceeded its protective role. The extract recorded anti-inflammatory, and antioxidant effects due to the presence of flavonoid compounds.

Combination of melatonin and certain drugs for treatment of diabetic nephropathy in streptozotocin-induced diabetes in rats.

Diabetic nephropathy is a major complication of diabetes and a leading cause of end-stage renal failure in many developed countries. The study aimed to evaluate the efficiency of certain drugs and melatonin in the treatment of nephropathy secondary to diabetes. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (50 mg/kg body weight). Three days after induction of diabetes (460-500 mg/dl), rats were treated daily for 60 days with Rowatinex, melatonin, Rowatinex + melatonin, Amosar (Losartan Potassium) (LSP) and LSP + melatonin. The evaluations were made by measuring blood urea nitrogen (BUN), serum uric acid, serum creatinine, urine creatinine, creatinine clearance, nitric oxide, malondialdehyde, superoxide dismutase, glutathione, total antioxidant capacity, kidney injury molecule-1, heat shock protein-70, caspase-3, transforming growth factor ß1, and DNA degradation by comet assay and total protein contents. The histopathological picture of the kidneys and pancreases was confirmed in our results. Diabetic rats showed drastic changes in all the measured parameters. Treatment with melatonin and the selected drugs revealed amelioration levels with variable degrees. In conclusion, the combination of LSP and melatonin had the most potent effect on treating the deleterious action of diabetes on rat kidney.