Antiarthritic activity of Physalis peruviana fruit extract via inhibition of inflammatory mediators: Integrated in vitro, in vivo and in silico study.

ETHNOPHARMACOLOGICAL RELEVANCE: P. peruviana fruit, native to Andean region, is cultivated worldwide for its adaptability to various soil natures and climatic conditions. It is increasingly consumed for its high nutritional profile and history of ethnomedical uses including treatment of arthritis. Little pharmacological evidences support this folk use except for previous in vitro study that reported significant inhibition of protein denaturation. AIM OF THE STUDY: The study aims at providing new in vivo evidence on antiarthritic activity of P. peruviana fruits in vivo that justifies its traditional use through mechanism-based experiment. MATERIAL AND METHODS: Inhibition of inflammatory mediators is considered one of the key treatments to alleviate painful symptoms of rheumatoid arthritis (RA). Anti-inflammatory activity was assessed against COX-1 and COX-2 activity in vitro. Serum TNFα, IL-1ß and IL-6 were traced using in vivo model of adjuvant-induced arthritis. Gross/inflammatory changes in rat paw, relative mass indices of spleen and liver were further investigated together with joint tissue histoarchitecture. Seven metabolites from different phytochemical classes, that were previously reported in P. peruviana fruit, were evaluated in silico against TNF-α target protein (PDB ID: 2AZ5) to assess their inhibitory effect. This was followed by assessment of their drug-likeness based on Lipinski's rule according to their physicochemical and pharmacokinetic properties. RESULTS: High dose of extract (E-1000 mg) improved adjuvant-induced cachexia and attenuated immune-inflammatory responses in paw and serum parameters, with equipotent effect to MTX, in addition to minimal side effect profile on spleen and liver. Histopathological study of knee joint tissues confirmed dose-dependent improvement in arthritic groups treated with P. peruviana fruit extracts. The insilico study recommended steroidal lactones withaperuvin E/C and hydroxywithanolide E as promising lead compounds for inhibiting TNF enzyme as evidenced by docking scores of 6.301, 5.488 and 5.763 kcal/mol, respectively, fitting as well the Lipinski's rule of drug likeness. CONCLUSION: The study provided novel approach that rationalize folk use of P. peruviana fruit in treatment of arthritis.

Characterization of biologically active exopolysaccharide produced by Streptomyces sp. NRCG4 and its anti-Alzheimer efficacy: in-vitro targets.

BACKGROUND: Exopolysaccharides are extremely powerful molecules with a wide range of uses in pharmaceuticals due to their structural and compositional complexity. Marine microorganisms often produce bioactive substances with novel functions and structures because of their special living conditions. Polysaccharides from marine microorganisms are of interest to new drug discovery. RESULTS: The current research focused on the isolation of bacteria from Red Sea, Egypt, that have the ability to produce a new natural exopolysaccharide in order to be examined in treating Alzheimer's illness to obviate side effects of synthetic drugs. Properties of exopolysaccharide (EPS) produced by an isolated Streptomyces strain were investigated for its capability to play as anti-Alzheimer. This strain was identified morphologically, physiologically, and biochemically and actually was confirmed by molecularly 16S rRNA analysis as Streptomyces sp. NRCG4 with accession number MK850242. The produced EPS was fractionated by precipitation 1:4 volumes of chilled ethanol and the third major fraction (1:3) listed as NRCG4, and then the functional groups, MW, and chemical evaluation have been detected via Fourier-transform infrared (FTIR), high-performance gel permeation chromatography (HPGPC), and high-performance liquid chromatography (HPLC). The findings showed that NRCG4 was an acidic EPS composed of mannuronic acid, glucose, mannose, and rhamnose in a molar ratio of 1.2:1.5:2.8:1.0, respectively. NRCG4 Mw was determined to be 4.25 × 105 gmol-1 and the Mn to be 1.97 × 105 gmol-1. Also, the NRCG4 included uronic acid (16.0%) and sulfate (0.0%), but no protein was found. In addition, antioxidant and anti-inflammation activity was measured through various methods. This study confirmed that NRCG4 exopolysaccharide exerted anti-Alzheimer's characters via inhibition of cholinesterase and tyrosinase as well as anti-inflammatory and antioxidant abilities. Additionally, it occurred a potential role in the suppression of Alzheimer's disease risk factors through its antioxidant (metal chelation, radical scavenging capability), anti-tyrosinase and anti-inflammatory characteristics. The anti-Alzheimer's disease efficacy of NRCG4 exopolysaccharide may be assigned to its unique determined chemical composition. CONCLUSIONS: The present study highlighted those exopolysaccharides could be harnessed to improve pharmaceutical industry (anti-Alzheimer, anti-tyrosinase, anti-inflammatory, and antioxidant agents).

Anticoagulant effect of Feijoa sellowiana extracts generated by different biotechnological techniques.

Blood clotting has become one of the most dangerous side effects associated with Corona virus, as well as the high level of cholesterol and triglycerides in the blood. Therefore, it has become necessary to use medicinal plants that are biologically safe and containing anti-clotting compound. Feijoa sellowiana represents a prolific source diverse compounds that may have thrombolytic activity. Therefore, the main research point is the production and scaling up of a target contents that have anticoagulants by using biotechnological techniques; calli production, and bioreactors and assessed their activity through in-vivo study. Murashige and Skoog (MS) medium enriched with varying concentrations of benzyl adenine (BA) and naphthalene acetic acid (NAA) was used to cultivate calli and cell suspension cultures from F. sellowiana seeds. Bioreactors were employed to boost active constituent's production. Moreover, the bioreactor physical factors such as effect of controlled or uncontrolled pH medium were investigated. The leaves of the main plant were extracted by ethanol 70% and polar and non-polar extracts were also prepared. The ethanol extract of calli and cells resulting from bioreactors were also prepared. All prepared extracts were subjected to chemical analysis by HPLC, in-vitro antioxidant assays, in-vivo anticoagulant activity and histopathological examination. Calli and cell suspension cultures were produced by using MS medium fortified with 1 mg/L BA+ 0.1 mg/L NAA. It was found that culturing of cell cultures in a bioreactor with uncontrolled pH and aeration at the value of 0.5 L/min gave the maximum and economical fresh and dry weights of the plants. After evaluation of all extracts; it was found that the calli ethanol extract for each plant was the highest value of total phenolic and total flavonoid contents either quantitatively or qualitatively. All extracts of Feijoa had antioxidant activity. The IC50 of the DPPH of Feijoa calli extract was 13.45 µg/mL, it was also confirmed by FRAP and ABTs values. Feijoa calli extract decreased platelet aggregation by suppression of thrombin, extended aPTT, PT, bleeding and clotting times. It was safer than warfarin medication. From these findings the authors can conclude that Feijoa had highly anticoagulant activity and the calli production achieved the goal of the enhancement of the phenolic constituent and thus their activity.

Innovative Processing Technologies to Develop a New Segment of Functional Citrus-Based Beverages: Current and Future Trends.

The food industries are interested in developing functional products due to their popularity within nutritional and healthy circles. Functional fruit-based beverages represent one of the fast-growing markets due to the high concentrations of bioactive compounds (BCs), which can be health promoters. Hence, functional beverages based on citrus fruits are a potential way to take advantage of their nutritional and bioactive properties that could attract the interest of consumers. In order to ensure microbial and quality stability, the beverages are subjected to preservation treatment; however, the application of high temperatures leads to the loss of thermolabile BCs. Nowadays, innovative processing technologies (IPT) such as pulsed electric field (PEF), high-pressure processing (HPP), ultrasound processing (US), ohmic heating (OH), and microwave (MW) are a promising alternative due to their efficiency and low impact on juice BCs. The available literature concerning the effects of these technologies in functional fruit-based beverages is scarce; thus, this review gathers the most relevant information about the main positive and negative aspects of the IPT in functional properties, safety, and consumer acceptance of functional citrus-based beverages, as well as the use of citrus by-products to promote the circular economy in citrus processing.

The suppressive role of nanoencapsulated chia oil against DMBA-induced breast cancer through oxidative stress repression and tumor genes expression modulation in rats.

BACKGROUND: Chia oil is high in omega-3 fatty acids, which have been linked to a lower risk of many diseases, including cancer. Oil encapsulation is a method that holds promise for maintaining oil content while enhancing solubility and stability. The purpose of this study is to prepare nanoencapsulated Chia oil and investigate its suppressive effects on rat chemically induced breast cancer. METHODS: The oil was extracted from commercial Chia seeds and their fatty acids were analyzed using Gas Chromatography-mass spectrometry (GC/MS). Sodium alginate was used as a loading agent to create the Chia oil nanocapsules. The DPPH assay was used to assess the oil nanocapsules' capacity to scavenge free radicals. Breast cancer induction was done by single dose subcutaneously administration of 80 mg/kg dimethylbenz (a) anthracene (DMBA). Models of breast cancer were given Chia oil nanocapsules orally for one month at doses of 100 and 200 mg/kg. Through measuring intracellular reactive oxygen species (ROS) and protein carbonyl, assessing the gene expression of tumor suppressor genes (BRCA 1 & 2, TP53), and conducting histopathological analysis, the suppressive effect of Chia oil nanocapsules was examined. RESULTS: The increase in ROS and PC levels brought on by DMBA was significantly decreased by the administration of Chia oil nanocapsules. In tumor tissue from rats given Chia oil nanocapsules, the mRNA expression levels of BRCA1, BRCA2, and TP53 were controlled Histopathological analysis clarified that the tissue architecture of breast tumors was improved by nanocapsules management. CONCLUSIONS: These findings demonstrate the ability of Chia oil nanocapsules to inhibit cancer cells in the rat breast.

Topiramate potential neurotoxicity and mitigating role of ginger oil in mice brain.

Topiramate has multiple pharmacological mechanisms that are efficient in treating epilepsy and migraine. Ginger has been established to have gingerols and shogaols that cause migraine relief. Moreover, Topiramate has many off-label uses. Thus, it was necessary to explore the possible neurotoxicity of Topiramate and the role of ginger oil in attenuating the Topiramate neurotoxicity. Male albino mice were orally gavaged with Topiramate, ginger oil (400 mg/kg), and Topiramate plus ginger oil with the same pattern for 28 days. Oxidative stress markers, acetylcholinesterase (AchE), gamma-aminobutyric acid (GABA), and tumor necrosis factor-alpha (TNF-α) were examined. Histopathological examination, immunohistochemical glial fibrillary acidic protein (GFAP), and Bax expression analysis were detected. The GABAAR subunits, Gabra1, Gabra3, and Gabra5 expression, were assessed by RT-qPCR. The investigation showed that Topiramate raised oxidative stress markers levels, neurotransmitters, TNF-α, and diminished glutathione (GSH). In addition, Topiramate exhibited various neuropathological alterations, strong Bax, and GFAP immune-reactivity in the cerebral cortex. At the same time, the results indicated that ginger oil had no neurotoxicity. The effect of Topiramate plus ginger oil alleviated the changes induced by Topiramate in the tested parameters. Both Topiramate and ginger oil upregulated the mRNA expression of gabra1 and gabra3, while their interaction markedly downregulated them. Therefore, it could be concluded that the Topiramate overdose could cause neurotoxicity, but the interaction with ginger oil may reduce Topiramate-induced neurotoxicity and should be taken in parallel.

Phytogenic compounds from avocado (Persea americana L.) extracts; antioxidant activity, amylase inhibitory activity, therapeutic potential of type 2 diabetes.

Diabetes is a worldwide public health disease. Currently, the most effective way to treat diabetes is to mitigate postprandial hyperglycemia by inhibiting carbohydrate hydrolysis enzymes in the digestive system. Plant extracts are rich in bioactive compounds, which can be used in diabetes treatment. This study aims to evaluate the polyphenols content in ethanolic extracts of avocado fruit and leaves (Persea americana Mill.). Additionally, their antioxidant activity using DPPH, while the inhibition ability of α-amylase was examined by reacting different amounts of the extracts with α-amylase compared to acarbose as standard inhibitor. The active compounds were detected in the extracts by LC/MS. The obtained results showed that the leaf extract recorded a significant content of total phenolic compounds compared to the fruit extract (178.95 and 145.7 mg GAE /g dry weight, respectively). The total flavonoid values ​​ranged from 32.5 to 70.08 mg QE/g dry weight of fruit and leaves extracts, respectively. Twenty-six phytogenic compounds were detected in leaf and fruit extract by LC/MS. These compounds belong to fatty acids, sterols, triterpenes, phenolic acids, and flavonoids. The antioxidant activity of the extracts is due to the exist of phytogenic compounds, i.e., polyphenols and flavonoids. The antioxidant activity increased in a concentration dependant manner. Avocado fruit extract (1000 µg/mL) scavenged 95% of DPPH while leaf extract rummaged 91.03% of free radicals compared with Vit C and BHT. Additionally, higher α-amylase inhibitory activity was observed in fruit extract than the leaf extract, where the fruit and leaf extract (1000 µg/ml) inhibited the enzyme by 92.13% and 88.95%, respectively. The obtained results showed that the ethanolic extracts of avocado could have a significant impact on human health due to their high content of polyphenols.

Genotoxic, biochemical and histopathological studies to assessment the topiramate hepatorenal toxicity in mice.

Liver and kidney role in detoxification and drug metabolism increases the risk of their poisonous injury. Topiramate (TMP) is an effective popular migraine prophylaxis that is accepted for utilize in adults and teenagers. Therefore, the target of this research is to estimate the potential toxic effects of TMP on liver and kidney in male mice. Thirty-two adult albino male mice were divided into four groups (n = 8 mice). Group I of animals was given saline solution and used as negative control. The other three groups were administrated TPM at doses (100, 200 and 400 mg/kg) for 28 days. Genotoxicity was evaluated by comet assay and DNA fragmentation by Diphenyleamine. Biochemical investigation was achieved by estimating liver enzymes (AST, ALT), alkaline phosphatase (ALP) creatinine and uric acid. In addition, measurement of the antioxidant enzymes, malondialdehyde and nitric oxide were performed in both two tissues of liver and kidney. Microscopic examination of hematoxyline and eosin (H&E), tumor necrosis factor (TNF-α) and caspase3 stained sections were done to explore the effect of topiramate on mice tissues of liver and kidney. The data revealed that TPM showed dose dependent toxicity that represented in: DNA damage in tested cells and increased level of liver enzymes, creatinine and uric acid as markers of toxicity. Topiramate significantly diminished antioxidant enzymes activities and elevated the level of malondialdehyde and nitric oxide. In addition, TPM caused histopathological alterations and dose dependent positive immune reaction for TNF--α and caspase 3 in kidney and liver tissues. The results showed that Topiramate has marked toxicity in liver and kidney of mice.

Eruca sativa seed extract modulates oxidative stress and apoptosis and up-regulates the expression of Bcl-2 and Bax genes in acrylamide-induced testicular dysfunction in rats.

Acrylamide (ACR) has been previously associated with male sexual dysfunction and infertility. Eruca sativa (L.) (arugula or rocket) have been widely used in traditional remedies in Mediterranean region and western Asia and was known for its strong aphrodisiac effect since Roman times. The current study was designed to investigate LC/MS analysis of total ethanol extract Eruca sativa (L.) and the efficiency and mechanism of action of Eruca sativa seed extract (ESS) in reducing hypogonadism induced by acrylamide in male rats. Male Wistar rats were divided into 6 groups (n = 7): control group, Eruca sativa seed extract (ESS) at doses of 100 and 200 mg\kg, acrylamide (ACR), ACR + ESS 100 mg/kg, and ACR + ESS 200 mg/kg. The animals received ACR at a dose of 10 mg/kg b.wt for 60 days. Sperm indices, testicular oxidative stress, testosterone hormone, and testicular histopathology and immunohistochemistry of PCNA and caspase-3 were investigated. Moreover, the expression level of testicular B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) genes was evaluated. In respect to the LC/MS of total ethanol extract Eruca sativa (L.) seed revealed tentative identification of 39 compounds, which belongs to different classes as sulphur-containing compounds, flavonoids, phenolic acid, and fatty acids. Administration of ESS extract (100, 200 mg/kg) improved semen quality, diminished lipid peroxidation, enhanced testicular antioxidant enzyme, restored serum testosterone level, and reduced testicular degeneration and Leydig cell death in the rats intoxicated with ACR. However, the effects of ESS at the dose of 200 mg/kg were similar to that of control group. Furthermore, ESS treatment significantly induced anti-apoptotic effect indicated by elevation of both Bcl-2 and Bax expressions. Nutriceutics of ESS extract protects testis against ACR-induced testicular toxicity via normalizing testicular steroidogenesis, keeping Leydig cells, and improving oxidative stress status.

Efficiency of turnip bioactive lipids in treating osteoporosis through activation of Osterix and suppression of Cathepsin K and TNF-α signaling in rats.

Vegetable oils are characterized by their bioactive phytochemicals including fatty acids, tocols, and phenolic compounds. In the current study, turnip (Brassica rapa) oil was evaluated for its fatty acid profiles, tocol composition, and total phenolic content. The radical scavenging properties of oil against DPPH· and galvinoxyl radicals were also evaluated. Turnip oil efficiency in treating osteoporosis was tested in rats. Fifty adult female Sprague-Dawley albino rats were divided to five groups (n = 10/group). An osteoporotic rat model was prepared by two separate 5-day (5 days on/9 days off) courses of methotrexate subcutaneous injection. Osteoporotic rats were orally gavaged with turnip oil (200 and 400 mg/kg/day) for 28 days. Turnip oil efficiency in treating osteoporosis was studied by evaluation of Osterix, Cath K, and TNF-α transcript expression levels that involved in bone remodeling in femoral bones. Minerals and vitamin D were estimated in blood serum. Femoral bone histological and morphometric analyses were investigated in osteoporotic and turnip oil-treated rats. In vitro assays revealed strong antiradical potential of turnip oil. Treatment with turnip oil regulated the levels of Osterix, Cath K, and TNF-α mRNA that was accompanied with elevating the levels of calcium, phosphorous, bone alkaline phosphatase (BALP), and vitamin D in osteoporotic rats. The histological and morphometric inspection revealed that turnip oil displayed progress in the osteoporotic rat bone formation that was clear in the enhancement of thickness of femur shaft cortical bone and femur head trabecular bone. Above-mentioned findings indicated that turnip oil has the potential to share in the treatment of osteoporosis.

Effect of antiepileptic drug (Topiramate) and cold pressed ginger oil on testicular genes expression, sexual hormones and histopathological alterations in mice.

Sexual dysfunction in the epileptic patient is difficult to confirm whether it is ailment or therapy related. Antiepileptic drugs often use in reproductive age, through reproductive progress and maturation. On the other side, cold-pressed oils are rich in bioactive phytochemicals with health-promoting traits. The target of this work was to appraise the sexual dysfunction of antiepileptic Topiramate (TPM) and cold pressed ginger oil (CPGO) as antiepileptic alternative medicine in male mice. Fifty-four adult male albino mice were divided into nine groups (n = 6 mice). One group given saline and used as negative control; another one was given corn oil as vehicle. Six groups administered orally with TPM or CPGO at 100, 200 and 400 mg/kg. Moreover, group of animals co-administrated orally CPGO with TPM (400 mg/kg) to study their interaction. Fatty acid profile and tocols composition of CPGO were determined. in vitro assays were undertaken to evaluate radical scavenging traits of CPGO utilizing sable 1,1-diphenyl-2-picrylhydrazyl (DPPH·) and galvinoxyl radicals. The study investigated antioxidant and oxidative stress markers, sexual hormones levels, mRNA levels of vascular endothelial growth factor (Vegfa), synaptonemal complex protein (Sycp3), Wilms tumor gene (Wt1) as well as histopathological and immunohistochemical examination. Strong radical scavenging potential of CPGO against stable DPPH· and galvinoxyl radicals was recorded. The results revealed that TPM caused a dose-dependent reduction in the antioxidant activities and testosterone content, while, malonaldehyde (MDA) and nitric oxide (NO) as oxidative stress markers were elevated. Vegfa and Sycp3 mRNA expression down-regulated at all Topiramate tested doses, but Wt1 up-regulated at 400 mg/kg. TPM (400 mg/kg) revealed histological alterations associated with strong positive Bax immune reactive spermatogoneal and Leydig cells. Ginger oil elevated the CAT and SOD (antioxidant enzymes), serum testosterone and diminished the oxidative stress, up regulated the expression of Vegfa and Sycp3 and down-regulated the Wt1 expression. Meanwhile, CPGO revealed no histopathological alterations and no Bax immune-reactive cells. CPGO co-administration with TPM (400 mg/kg) attenuated the TPM toxicity. High doses of TPM may exhibit sexual dysfunction but CPGO is safe and has androgenic property. CPGO co-administration could protect the antiepileptic patient from the TPM sexual dysfunction.

Evaluation of the alleviative role of Chlorella vulgaris and Spirulina platensis extract against ovarian dysfunctions induced by monosodium glutamate in mice.

Microalgae provide a wealthy natural resource of bioactive compounds, which have many biological activities. Monosodium glutamate is a food additive that acts either as food preservatives or as tastiness enhancer. It was confirmed that monosodium glutamate poses a serious responsibility in the pathogenesis of anovulatory infertility. Therefore, the idea of this research was directed to reveal efficiency of Chlorella vulgaris and Spirulina platensis extracts against the ovarian dysfunction resulted due to monosodium glutamate consumption. Adult female albino mice were gavages orally monosodium glutamate alone or with either Chlorella vulgaris or Spirulina platensis aqueous extracts for 28 days. Female mice were subjected to superovulation to study the oocytes nuclear maturation stages. Histological and quantitative investigation was carried on ovaries. Biochemical assessment to measure the sex hormones level and ovarian enzymatic antioxidants was done. In addition, ovarian antioxidant mRNA genes were determined using quantitative PCR and Glyceraldehyde-3-phosphate dehydrogenase was used as an internal control. The result revealed that monosodium glutamate reduced the oocytes quality and maturation rate, while, both algae improve the oocyte quality and maturation rate than in monosodium glutamate group. Chlorella vulgaris and Spirulina platensis improved the monosodium glutamate ovarian tissue histological alteration, sex hormones content and raised the ovarian enzymatic antioxidants level. In addition, monosodium glutamate markedly diminished the Glutathione peroxidase, superoxide dismutase and catalase mRNA expressions, However, Chlorella vulgaris or Spirulina platensis upregulated the expression of genes close to control. In conclusion, Chlorella vulgaris and Spirulina platensis showed potential alleviative role against the monosodium glutamate ovarian dysfunction.

Biochemical characterization, anti-inflammatory properties and ulcerogenic traits of some cold-pressed oils in experimental animals.

CONTEXT: Cold-pressed oils (CPO) are commercially available in the market and characterized by their health-promoting properties. OBJECTIVE: Clove oil (CLO), coriander seed oil (COO) and black cumin oil (BCO) were evaluated for their bioactive lipids. Pharmacological screening was performed to evaluate acute toxicity, anti-inflammatory and ulcerogenic effects as well as histopathological changes in tissues of albino rats fed with CPO. MATERIALS AND METHODS: Fatty acids, tocols and total phenolics were analyzed. The acute toxicity test for each CPO was estimated during 14 d. Carrageenan-induced rat paw oedema was used for assessment of anti-inflammatory activity of CPO. Animals were fasted overnight, and via oral gavage given indomethacin (10 mg/kg) or CPO (400 mg/kg) to investigate ulcerogenecity. Histopathological changes in liver, kidney, heart, spleen and stomach were screened. RESULTS: Amounts of α-, ß-, γ- and δ-tocopherols in CLO were 1495, 58, 4177 and 177 mg/kg oil, respectively. In COO, α, ß, γ and δ-tocopherols were 10.0, 18.2, 5.1 and 34.8%, respectively. In BCO, ß-tocotrienol was the main constituent. CLO, COO and BCO contained 4.6, 4.2 and 3.6 mg GAE/g, respectively. Acute toxicity test determined that 400 mg/kg of CPO to be used. In the carrageenan model of inflammation, pretreatment of rats with indomethacin (10 mg/kg) or CLO (400 mg/kg) induced a significant (p < 0.05) reduction by 31.3 and 27.4%, respectively, in rat paw oedema as compared with the carrageenan-treated group. Indomethacin induced a significant ulcerogenic effect with an ulcer index of 19. Oral treatment of CPO showed no ulcerogenic effect, wherein no histopathological changes were observed. CONCLUSIONS: CPO, particularly CLO, could minimize acute inflammation.

Protective Effect of Ethanolic Extract of Grape Pomace against the Adverse Effects of Cypermethrin on Weanling Female Rats.

The adverse effect of cypermethrin on the liver and kidney of weanling female rats and the protective effect of ethanolic extract of grape pomace were investigated in the present study. Weanling female rats were given cypermethrin oral at a dose of 25 mg kg(-1) body weight for 28 consecutive days. An additional two Cyp-trated groups received extract at a dose of 100 and 200 mg kg(-1) body weight, respectively, throughout the experimental duration. Three groups more served as extract and control groups. Administration of Cyp resulted in a significant increase in serum marker enzymes, for example, aminotransferases (AST and ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT), and increases the level of urea nitrogen and creatinine. In contrast, Cyp caused significant decrease in levels of total protein and albumin and caused histopathological alterations in liver and kidneys of female rats. Coadministration of the extract to Cyp-treated female rats restored most of these biochemical parameters to within normal levels especially at high dose of extract. However, extract administration to Cyp-treated rats resulted in overall improvement in liver and kidney damage. This study demonstrated the adverse biohistological effects of Cyp on the liver and kidney of weanling female rats. The grape pomace extract administration prevented the toxic effect of Cyp on the above serum parameters. The present study concludes that grape pomace extract has significant antioxidant and hepatorenal protective activity.