Crosstalk between protein misfolding and endoplasmic reticulum stress during ageing and their role in age-related disorders.

Maintaining the proteome is crucial to retaining cell functionality and response to multiple intrinsic and extrinsic stressors. Protein misfolding increased the endoplasmic reticulum (ER) stress and activated the adaptive unfolded protein response (UPR) to restore cell homeostasis. Apoptosis occurs when ER stress is prolonged or the adaptive response fails. In healthy young cells, the ratio of protein folding machinery to quantities of misfolded proteins is balanced under normal circumstances. However, the age-related deterioration of the complex systems for handling protein misfolding is accompanied by ageing-related disruption of protein homeostasis, which results in the build-up of misfolded and aggregated proteins. This ultimately results in decreased cell viability and forms the basis of common age-related diseases called protein misfolding diseases. Proteins or protein fragments convert from their ordinarily soluble forms to insoluble fibrils or plaques in many of these disorders, which build up in various organs such as the liver, brain, or spleen. Alzheimer's, Parkinson's, type II diabetes, and cancer are diseases in this group commonly manifest in later life. Thus, protein misfolding and its prevention by chaperones and different degradation paths are becoming understood from molecular perspectives. Proteodynamics information will likely affect future interventional techniques to combat cellular stress and support healthy ageing by avoiding and treating protein conformational disorders. This review provides an overview of the diverse proteostasis machinery, protein misfolding, and ER stress involvement, which activates the UPR sensors. Here, we will discuss the crosstalk between protein misfolding and ER stress and their role in developing age-related diseases.

Standardized Polyalthia longifolia leaf extract induces the apoptotic HeLa cells death via microRNA regulation: identification, validation, and therapeutic potential.

Polyalthia longifolia var. angustifolia Thw. (Annonaceae), is a famous traditional medicinal plant in Asia. Ample data specifies that the medicinal plant P. longifolia has anticancer activity; however, the detailed mechanisms of action still need to be well studied. Recent studies have revealed the cytotoxicity potential of P. longifolia leaf against HeLa cells. Therefore, the current study was conducted to examine the regulation of miRNAs in HeLa cancer cells treated with the standardized P. longifolia methanolic leaf extract (PLME). The regulation of miRNAs in HeLa cancer cells treated with the standardized PLME extract was studied through Illumina, Hi-Seq. 2000 platform of Next-Generation Sequencing (NGS) and various in silico bioinformatics tools. The PLME treatment regulated a subset of miRNAs in HeLa cells. Interestingly, the PLME treatment against HeLa cancer cells identified 10 upregulated and 43 downregulated (p < 0.05) miRNAs associated with apoptosis induction. Gene ontology (GO) term analysis indicated that PLME induces cell death in HeLa cells by inducing the pro-apoptotic genes. Moreover, the downregulated oncomiRs modulated by PLME treatment in HeLa cells were identified, targeting apoptosis-related genes through gene ontology and pathway analysis. The LC-ESI-MS/MS analysis identified the presence of Vidarabine and Anandamide compounds that were previously reported to exhibit anticancer activity. The findings of this study obviously linked the cell cytotoxicity effect of PLME treatment against the HeLa cells with regulating various miRNAs expression related to apoptosis induction in the HeLa cells. PLME treatment induced apoptotic HeLa cell death mechanism by regulating multiple miRNAs. The identified miRNAs regulated by PLME may provide further insight into the mechanisms that play a critical role in cervical cancer, as well as novel ideas regarding gene therapeutic strategies.

GC-MS-based profiling and ameliorative potential of Carissa opaca Stapf ex Haines fruit against cardiac and testicular toxicity: An In vivo study.

Fruit of Carissa opaca Stapf ex Haines (C. opaca) is a feed additive and is commonly used against cardiac dysfunction, fever, asthma, diarrhea, gastrointestinal ailments, and skin diseases. In this study, we aimed to evaluate the metabolic profile and antioxidant potential of C. opaca fruit against carbon tetrachloride (CCl4)-induced cardiotoxicity and testicular toxicity in rats. Gas Chromatoghraphy-Mass Spectrometry (GC-MS) analysis of C. opaca fruit for the identification of potential metabolic profile, followed by methanolic extract of C. opaca and its derived fractions including n-hexane, ethyl acetate, chloroform, butanol, and aqueous were used to assess the antioxidant potential of fruits. Ten groups of rats received different treatments and got evaluated for cardiac and testicular antioxidant enzymes, histological architecture, and serum hormonal levels. GC-MS analysis of methanolic extract of C. opaca fruit showed the presence of some bioactive metabolites like cyclodecane, diethyl 2,6-pyridine dicarboxylate, tetrahydro-geraniol, S-[2-[N, N-Dimethylamino]ethyl]morpoline, 2,3-Methylenedioxyphenol, alpha-d-Glucopyranoside, 5,10-Diethoxy-2,3,7,8-tetrahydro-1H, 6H-dipyrrolo [1,2-a; 1',2'-d] pyrazine and 1,3-Benzothiazol-2(3H)-one,3-(3,3-dimethyl-1-oxobutyl) that corresponds the medicinal properties of C. opaca fruit. Prepared fractions of C. opaca fruits mitigated the toxicity induced by CCl4 in the heart and testicular tissues of rats. Oxidative stress was caused by the inhibition of activities of glutathione and other antioxidant enzymes of the body, while on the other hand elevating the levels of nitrite and hydrogen peroxide. Treatment with C. opaca fruit extract normalized the levels of enzymes, reproductive hormones, and free radicals thus restoring the histopathological and enzymatic biomarkers towards the normal group. The study supports the indigenous use of fruits as an alternative medicine against cardiac dysfunction by providing scientific evidence of protection against CCl4-induced injuries, and it also concludes the antioxidant defensive role in testicular tissues.

Pleurospermum candollei Methanolic Extract Ameliorates CCl4-Induced Liver Injury by Modulating Oxidative Stress, Inflammatory, and Apoptotic Markers in Rats.

The main objective of this study was to investigate the hepatoprotective potency of the Pleurospermum candollei methanol extract against CCl4-induced liver damage in rats. HPLC technique was used to estimate the presence of polyphenols in the methanol extract of P. candollei (PCM), while proximate analysis revealed the presence of carbohydrates, lipids, and moisture in the extract. The antioxidant potential of PCM was evaluated by 2,2-diphenylpicrylhydrazyl (DPPH) and reducing power assay, which showed a high percentage of inhibition against free radicals. Hepatotoxicity was induced by carbon tetrachloride (CCl4). CCl4 administration reduced the activity of endogenous antioxidants, whereas it increased the production of nitrites and hydrogen peroxide (H2O2) in rats. Furthermore, the level of hepatic markers in serum was also elevated after CCl4 administration. Moreover, the expression of stress-related markers, proinflammatory mediators, and apoptotic genes was enhanced in CCl4-treated rats. Coadministration of PCM along with CCl4 in rats reduced the levels of free radicals and the above genes to normal levels. CCl4 administration caused histopathological alterations in liver tissues, while cotreatment with PCM mitigated liver injuries. These findings suggest that the methanol extract of P. candollei possesses antioxidant and anti-inflammatory properties and can prevent liver injury. Further pharmacological research will be helpful in determining the effectiveness of P. candollei in humans. Development of FDA-approved plant-based anti-inflammatory drugs can help treat patients and reduce the chances of toxicity.

Synergistic Antimicrobial Activity of Ceftriaxone and Polyalthia longifolia Methanol (MEPL) Leaf Extract against Methicillin-Resistant Staphylococcus aureus and Modulation of mecA Gene Presence.

Medicinal plants are an essential source of traditional curatives for numerous skin diseases. Polyalthia longifolia (Sonn.) Thwaites (Annonaceae family) is a medicinal plant used to cure skin illnesses. P. longifolia is usually applied in folkloric therapeutical systems to treat skin diseases. The methicillin-resistant Staphylococcus aureus (MRSA) bacteria is among the essential bacteria contributing to skin diseases. Hence, to verify the traditional medicinal claim of P. longifolia usage in skin disease treatment, the current research was performed to study the synergistic antibacterial activity of standardized Polyalthia longifolia methanol leaf extract (MEPL) against MRSA bacteria. The synergistic antimicrobial activity result of ceftriaxone, when mixed with MEPL, against MRSA was investigated by the disc diffusion method, broth microdilution method, checkerboard dilution test, and modulation of mecA gene expression by multiplex polymerase chain reaction (multiplex PCR). The MEPL extract exhibited good synergistic antimicrobial activity against MRSA. Using the checkerboard method, we confirmed the synergistic effect of MEPL from P. longifolia and ceftriaxone (2:1) for MRSA with a marked reduction of the MIC value of the ceftriaxone from 8000 µg/mL to 1000 µg/mL. Moreover, the combination of MEPL with ceftriaxone significantly (p < 0.05) inhibited the presence of the resistant mecA gene in the tested strain. The LC-ESI-MS/MS analysis identified compounds that were reported to exhibit antimicrobial activity. Conclusively, the MEPL extract, an important etiological agent for skin diseases, showed worthy synergistic antimicrobial action against MRSA bacteria, thus supporting the traditional use of P. longifolia.

Green Carbon Dots: Synthesis, Characterization, Properties and Biomedical Applications.

Carbon dots (CDs) are a new category of crystalline, quasi-spherical fluorescence, "zero-dimensional" carbon nanomaterials with a spatial size between 1 nm to 10 nm and have gained widespread attention in recent years. Green CDs are carbon dots synthesised from renewable biomass such as agro-waste, plants or medicinal plants and other organic biomaterials. Plant-mediated synthesis of CDs is a green chemistry approach that connects nanotechnology with the green synthesis of CDs. Notably, CDs made with green technology are economical and far superior to those manufactured with physicochemical methods due to their exclusive benefits, such as being affordable, having high stability, having a simple protocol, and being safer and eco-benign. Green CDs can be synthesized by using ultrasonic strategy, chemical oxidation, carbonization, solvothermal and hydrothermal processes, and microwave irradiation using various plant-based organic resources. CDs made by green technology have diverse applications in biomedical fields such as bioimaging, biosensing and nanomedicine, which are ascribed to their unique properties, including excellent luminescence effect, strong stability and good biocompatibility. This review mainly focuses on green CDs synthesis, characterization techniques, beneficial properties of plant resource-based green CDs and their biomedical applications. This review article also looks at the research gaps and future research directions for the continuous deepening of the exploration of green CDs.

Efficacy of citric acid chelate and Bacillus sp. in amelioration of cadmium and chromium toxicity in wheat.

Heavy metals contamination in agricultural soil is a major issue having drastic effects on plants and human health. To solve this issue, we have formulated and tested a new approach of fusion of inorganic (citric acid chelate) and organic (Bacillus sp.) amelioration methods for heavy metals. The Bacillus sp. was heavy metal tolerant and showed plant growth-promoting characteristics including phosphate solubilization, siderophore production, hydrogen cyanide production, indole acetic acid production, and 1-Aminocyclopropane-1-carboxylate deaminase production. The analysis of data showed that plants receiving the combined application of citric acid (CA) chelate and Bacillus sp. mitigated heavy metal toxicity. They augmented the biomass production and amount of photosynthetic pigments in plant cells. They suppressed the negative effects of Cadmium (Cd) and Chromium (Cr) on plants' metabolic systems. A considerable increase was also observed in the activity of enzymatic and non-enzymatic antioxidants which reduced the damaging effects of reactive oxygen species and maintained internal structures of cells. The decrease in the content of Cr and Cd in wheat grains by the treatment of CA chelate and Bacillus sp. was 51%, and 27% respectively. The bioaccumulation of metals was also reduced to 49% (Cr) and 57% (Cd). This approach can be tested and applied in field conditions for soils with heavy metals contamination.

Evaluation of antioxidant profile of various solvent extracts of Carissa opaca leaves: an edible plant.

BACKGROUND: Carissa opaca leaves were conventionally recommended by local hakims in Pakistan for curing various human diseases including renal, hepatic and jaundice. In this work we arranged to study the antioxidant status of various fractions of C. opaca leaves through nine multifaceted assay systems. METHODS: Various fractions were prepared through solvent-solvent extraction technique on the basis of their polarity. The fractions were screened via different free radicals viz; DPPH·, ABTS·+,OH·, O2·, iron chelating and hydrogen peroxide assays. Total concentrations of phenolic content (TPC) and flavonoids were studied. RESULTS: Various fractions of C. opaca leaves showed significant activities against the tested reactive free radicals. The C. opaca was shown to have the highest TPCs with lowest EC50 values for the DPPH·, ABTS·+ radical scavenging capacities and iron chelating scavenging efficiency, moreover, C. opaca had best activities in scavenging of superoxide radicals and hydrogen peroxide as well as potently scavenged the hydroxyl radicals. CONCLUSION: These results suggest the potential of C. opaca leaves as a medicine against free-radical-associated oxidative damage.

Evaluation of Rumex hastatus leaves against hepatic fibrosis: a rat model.

BACKGROUND: Rumex hastatus leaves have been widely used as food additive and for the treatment of various liver ailments. According to our previous studies, ethyle acetate (ERL) and methanolic (MRL) fractions of R. hastatus leaves are an accessible source of natural antioxidants. In the present research work we arranged to investigate the R. hastatus leaves as hepaptoprotective agent verse hepatic damages caused by CCl4. METHODS: During this project we divided 48 rats into eight groups randomly. CCl4-induced damages were assessed through liver function markers viz.; alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), γ-glutamyltransferase (γ-GT) and lactate dehydrogenase (LDH). Changes in lipid profile were checked by measuring serum total cholesterol (TC), triglycerides (Tg), high density lipoproteins (HDL) and low density lipoproteins (LDL). Antioxidant status was checked by the activities of antioxidant enzymes, DNA damages and cellular abnormalities at histo level. RESULTS: Administration of CCl4 in rats caused significant increase in liver function and lipid profile indicating hepatic damages which were restored by co-administration of R. hastatus extracts. Cellular and DNA damages in hepatic tissues were caused by CCl4 which shown clear hepatic fibrosis in addition to disturb antioxidant enzyme level. Co-treatment with various fractions of R. hastatus leaves regulated these markers of oxidative dysfunctions. CONCLUSION: From the present report it was inferred that R. hastatus leaves have the ability to reverse CCl4 - induced hepatic damages.

Effect of Launaea procumbens extract on oxidative marker, p53, and CYP 2E1: a randomized control study.

BACKGROUND: Ethyl acetate extracts of Launaea procumbens is used for the treatment of liver dysfunction as an herbal medicine in Pakistan. In this study, the protective effects of ethyl acetate extracts were evaluated against CCl4-induced liver injuries in rat. METHODS: To examine the protective effects against oxidative stress of carbon tetrachloride in rats, 30 male rats were equally divided into 5 groups (6 rats). Among five groups, one was treated with CCl4 (3 ml/kg i.p. in olive oil b.w.) twice a week for 4 weeks. Others were orally fed with extracts (100, 200 mg/kg b.w.), with CCl4 twice a week for 4 weeks. RESULTS: Administration of CCl4 altered the serum marker enzymes, lipid profile, CYP 2E1, p53 expression, antioxidant enzymes, nuclear organizer regions (AgNORs), and DNA. Supplement of L. procumbens ameliorated the effects of CCl4, improved CYP 2E1, p53, and increased the activities of antioxidant enzymes while activity of liver marker enzymes (ALP, ALT, AST, g-GT) and contents of lipid per oxidation contents (TBARS), AgNORs, and DNA fragmentation were decreased. Similarly body weight was increased while liver and relative liver weight was decreased with co-administration of various extracts, suggesting that L. procumbens effectively protect liver against the CCl4-induced oxidative damage in rats. CONCLUSION: The hepatoprotective and free radical scavenging effects might be due to the presence of bioactive constituents in the extract.

Antitumor characterization of various fractions of Launaea procumbens.

The antitumor activity of various six fractions of Launaea procumbens were studied using the potato disk bioassay technique. Three concentrations (10, 100, and 1000 ppm) of all these six fractions were used for characterization of antitumor activity. Among these fractions, methanolic fraction exhibited significant inhibition of crown gall tumors caused by Agrobacterium tumefaciens followed by butanolic fraction. These results revealed that methanolic and butanolic fractions contain bioactive constituents responsible for inhibition of tumor. Further purification and characterization are in progress in our laboratory.

Protective effects of Carissa opaca fruits against CCl4-induced oxidative kidney lipid peroxidation and trauma in rat.

BACKGROUND: Carbon tetrachloride (CCl4) is a potent nephrotoxin, as it causes acute as well as chronic toxicity in kidneys. Therefore, this study was carried out to assess the pharmacological potential of different fractions of Carissa opaca fruits on CCl4-induced oxidative trauma in the kidney. METHODS: The parameters studied in this respect were the kidney function tests viz, serum profile, urine profile, genotoxicity, characteristic morphological findings, and antioxidant enzymatic level of kidneys. RESULT: The protective effects of various fractions of C. opaca fruits against CCl4 administration were reviewed by rat renal function alterations. Chronic toxicity caused by 8-week treatment of CCl4 to the rats significantly decreased the pH level, activities of antioxidant enzymes, and glutathione contents, whereas a significant increase was found in the case of specific gravity, red blood cells, white blood cells, level of urea, and lipid peroxidation in comparison to control group. Administration of various fractions of C. opaca fruit with CCl4 showed protective ability against CCl4 intoxication by restoring the urine profile, activities of antioxidant enzymes, and lipid peroxidation in rat. CCl4 induction in rats also caused DNA fragmentation and glomerular atrophy by means of dilation, disappearance of Bowmen's space, congestion in the capillary loops, dilation in renal tubules, and foamy look of epithelial cells of tubular region, which were restored by co-admiration of various fractions of C. opaca. CONCLUSION: Results revealed that the methanolic fractions of C. opaca are the most potent and helpful in kidney trauma.

Evaluation of phytochemical content, antimicrobial, cytotoxic and antitumor activities of extract from Rumex hastatus D. Don roots.

BACKGROUND: Being a part of Chinese as well as ayurdic herbal system, roots of Rumex hastatus D. Don (RH) is highly medicinal, used to regulated blood pressure. It is also reported that the plant is diuretic, laxative, tonic, used against microbial skin diseases, bilious complaints and jaundice. The present study is conducted to evaluate phytochemical, antimicrobial, antitumor and cytotoxic activities of extract obtained from R. hastatus roots. METHODS: RH roots were powdered and extracted with methanol to get crude extract. Crude extract was further fractioned on the basis of increasing polarity, with n-hexane (HRR), chloroform (CRR), ethyl acetate (ERR), n-butanol (BRR) and residual aqueous fraction (ARR). Methanol extract and its derived fractions were subjected to phytochemical screening and assayed for antibacterial activities via agar well diffusion method. Antifungal activities were checked through agar tube dilution method whereas potato disc assay was employed for the determination of antitumor activity. On the other hand cytotoxic activities were conducted using brine shrimps procedures. RESULTS: The results obtained from phytochemical analysis indicate the presence of alkaloids, anthraquinones, flavonoids and saponins in all the fractions. Most of the plant fractions showed substantial antimicrobial activities, which is in accordance with the spacious use of tested plant samples in primary healthcare center. Fractions of R. hastatus roots for cytotoxicity were tested as an effective cytotoxic was found as BRR > MRR > CRR > ARR > ERR > HRR. Ranking order of fractions of R. hastatus roots for effective antitumor screening was found as MRR > BRR > ARR > CRR > ERR > HRR. CONCLUSIONS: These results showed that R. hastatus appeared as an important source for the discovery of new antimicrobial drugs and antitumor agents; verify its traditional uses and its exploitation as therapeutic agent.

Carbon tetrachloride-induced lipid peroxidation and hyperglycemia in rat: a novel study.

Launaea procumbens methanol extract (LPME) was evaluated against carbon tetrachloride (CCl4)-induced pancreatic oxidative damage and hyperglycemia in rats. Various doses of the extract were administered to rats after 48 h of CCl4 treatment (3 ml/kg bodyweight (bw); intraperitoneally, 20% CCl4/olive oil) twice a week for 4 weeks. Coadministration of various concentrations of LPME (100, 150 and 200 mg/kg) ameliorated the toxicity of CCl4 and reversed the serum level of enzymes (amylase and lipase), glucose and hormone (insulin). The extract was able to reduce thiobarbituric acid reactive substance but increased the glutathione contents in pancreatic tissue. Depletion of antioxidant enzyme activities (catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase and glutathione-S-reductase) and DNA damages induced with CCl4 were restored by LPME supplement. It is suggested that LPME effectively protects the liver against the CCl4-induced oxidative damage in rats, possibly through antioxidant and/or free radical scavenging effects of flavonoids and phenolic compounds in the extract.

Modulation of carbon tetrachloride-induced nephrotoxicity in rats by n-hexane extract of Sonchus asper.

Sonchus asper is traditionally used in the treatment of renal dysfunction. In the present study, protective effects of S. asper against carbon tetrachloride (CCl4)-induced nephrotoxicity of rats were determined. In this study, 24 male albino rats (190-200 g) were equally divided into four groups. Group I (control group) was given saline (1 ml/kg body weight (b.w.), 0.85% NaCl) and dimethyl sulfoxide (1 ml/kg b.w.); group II was treated with CCl4 (1 ml/kg b.w. intraperitoneally); groups III and IV were administered with CCl4 and after 48 h with S. asper n-hexane extract (SHE; 100 and 200 mg/kg b.w.). All the treatments were given twice a week for 4 weeks. The results revealed that CCl4-induced oxidative stress as evidenced by the significant depletion of antioxidant enzymes, namely, superoxide dismutase, catalase, peroxidase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, and glutathione contents, while increased lipid peroxidation (thiobarbituric acid-reactive substances contents). Administration of SHE significantly ameliorated (p < 0.01) the activity of antioxidant enzymes and reduced lipid peroxides. Coadministration revealed that S. asper extract can protect the kidney against CCl4-mediated oxidative damage by restoring the activity of antioxidant enzyme, due to the presence of plant bioactive constituents.

CCl4 induced genotoxicity and DNA oxidative damages in rats: hepatoprotective effect of Sonchus arvensis.

BACKGROUND: Sonchus arvesis is traditionally reported in various human ailments including hepatotoxicity in Pakistan. Presently we designed to assess the protective effects of methanolic extract of Sonchus arvesis against carbon tetrachloride induced genotoxicity and DNA oxidative damages in hepatic tissues of experimental rats. METHODS: 36 male Sprague-Dawley rats were randomly divided into 6 groups to evaluate the hepatoprotective effects of Sonchus arvensis against CCl4 induced genotoxicity, DNA damages and antioxidant depletion. Rats of normal control group were given free access of food and water add labitum. Group II rats received 3 ml/kg of CCl4 (30% in olive oil v/v) via the intraperitoneal route twice a week for four weeks. Group III and IV received 1 ml of 100 mg/kg b.w. and 200 mg/kg b.w. SME via gavage after 48 h of CCl4 treatment whereas group V was given 1 ml of silymarin (100 mg/kg b.w.) after 48 h of CCl4 treatment. Group VI only received 200 mg/kg b.w. SME. Protective effects of SME were checked by measuring serum markers, activities of antioxidant enzymes, genotoxicity and DNA dmages. RESULTS: Results of the present study showed that treatment of SME reversed the activities of serum marker enzymes and cholesterol profile as depleted with CCl4 treatment. Activities of endogenous antioxidant enzymes of liver tissue homogenate; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSHpx), glutathione-S-transferase (GST) and glutathione reductase (GSR) were reduced with administration of CCl4, which were returned to the control level with SME treatment. CCl4-induced hepatic cirrhosis decreased hepatic glutathione (GSH) and increased lipid peroxidative products (TBARS), were normalized by treatment with SME. Moreover, administration of CCl4 caused genotoxicity and DNA fragmentation which were significantly restored towards the normal level with SME. CONCLUSION: These results reveal that treatment of SME may be useful in the prevention of hepatic stress.

Cardioprotective role of leaves extracts of Carissa opaca against CCl4 induced toxicity in rats.

BACKGROUND: Carissa opaca are used traditionally in Pakistan for the treatment of various human ailments. Therefore, the study is arranged out to assess the cardio protective potential of different fractions of Carissa opaca leaves on CCl4-induced oxidative trauma in kidney. METHODS: The parameters studied in this respect were the cardiac function test (CK (U/l), CKMB (U/l), genotoxicity (% DNA fragmentation), characteristic morphological findings and antioxidant enzymatic level of cardiac tissue homogenate. RESULT: The protective effects of various fractions of Carissa opaca (C. opaca) leaves extract against CCl4 administration was reviewed by rat cardiac functions alterations. Chronic toxicity caused by eight week treatment of CCl4 to the rats significantly changed the cardiac function test, decreased the activities of antioxidant enzymes and glutathione contents whereas significant increase was found in lipid peroxidation comparative to control group. Administration of various fractions of C. opaca leaves extract with CCl4 showed protective ability against CCl4 intoxication by restoring the cardiac functions alterations, activities of antioxidant enzymes and lipid peroxidation in rat. CCl4 induction in rats also caused DNA fragmentation and histopathalogical abnormalities which were restored by co-admistration of various fraction of C. opaca leaves extract. CONCLUSION: Results revealed that various fraction of C. opaca are helpful in cardiac dysfunctions.

Effects of Carissa opaca fruits extracts on oxidative pulmonary damages and fibrosis in rats.

BACKGROUND: Carissa opaca is a Pakistani fruit, traditionally used in the treatment of various human ailments including asthma and pulmonary damage. The present study investigated the protective effects of Carissa opaca against CCl4-induced oxidative stress in rat lungs. METHODS: To assess the protective effects of Carissa opaca, 42 Sprague-Dawley male rats (170-180 g) were randomly divided into 7 groups. Group I was untreated and group II received olive oil intraperitoneally (i.p.) and dimethyl sulfoxide orally. Groups III, IV, V, VI and VII were administered CCl4, 3 ml/kg bodyweight (30% in olive oil i.p.). Group IV was administered 50 mg/kg bodyweight silymarin whereas groups V, VI and VII were treated with 200 mg/kg of various fractions of Carissa opaca after 48 h of CCl4 treatment for eight weeks. Antioxidant profiles in lungs were evaluated by estimating the activities of antioxidant enzymes: catalase, peroxidase, superoxide dismutase, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, quinone reductase and reduced glutathione. CCl4-induced lipid peroxidation was determined by measuring the level of thiobarbituric acid reactive substances (TBARS) with conjugation of DNA damage and histopathology. RESULTS: Administration of CCl4 for 8 weeks significantly reduced (p < 0.05) the activities of antioxidant enzymes and GSH concentration while increasing TBARS content and DNA damage. Co-treatment of various fractions of Carissa opaca and silymarin restored the activities of antioxidant enzymes and glutathione content. Changes in TBARS concentration and DNA fragmentation was significantly decreased (p < 0.05) following Carissa opaca and silymarin treatment in lung. CONCLUSIONS: Histopathological changes in rat lungs induced by CCl4 were significantly restored by co-treatment with Carissa opaca and silymarin.

Comprehensive assessment of phenolics and antiradical potential of Rumex hastatus D. Don. roots.

BACKGROUND: Roots of Rumex hastatus (Polygonaceae) are traditionally used for the treatment of various ailments including liver and lung diseases. In this study, various solvent extracts of R. hastatus roots, like methanolic, n-hexane, ethyl acetate, chloroform, butanol and aqueous fractions were assessed through their antioxidant properties in vitro and determination of phenolic contents. METHODS: Several parameters like DPPH˙, ABTS˙(+), ˙OH, H2O2, superoxide free radical scavenging, iron chelating power, reducing power, ß-carotene bleaching power, antioxidant capacity and total phenolics and flavonoids were evaluated. High Performance liquid Chromatography (HPLC) was also considered. RESULTS: Though all the fractions exhibited dose dependant activity. The samples with the highest activity were the butanol and methanol fractions in all the assays except hydrogen peroxide radical scavenging assay where chloroform fraction showed the highest scavenging aptitude. On the other hand, aquous fraction showed significant beta carotene linoleic acid, while n-hexane and ethyl acetate fractions exhibited a lesser antioxidant activity in all the assays. HPLC revealed the presence of rutin, luteolin-7-glucoside, vitexin and luteolin. CONCLUSION: These results have to some extent substantiated the use of R. hastatus roots against different diseases, as an excellent basis of potential antioxidant due to the presence of sufficient amount of phenolics such as rutin and luteolin.

Estimation of flavoniods, antimicrobial, antitumor and anticancer activity of Carissa opaca fruits.

BACKGROUND: Carissa opaca Stapf ex Hanes fruits is traditionally used in the treatment of asthma, hepatitis and microbial infections. The present study was arranged to investigate the antimicrobial, cytotoxic and antitumor activity of various fractions of C. opaca extract and its bioactive metabolites responsible for that activity. METHODS: To characterize various fractions of C.opaca antibacterial, antifungal, cytotoxic and antitumor assays are used. Eight strains of bacteria including Bacillus subtilis, Enterobactor aerogenes, Escherichia coli, Klebsiella pneumoniae, Micrococcus luteus, Pseudomonas aeroginosa, Salmonella typhy, and Staphylococcus aureus and four strains of fungal viz: Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger and Fusarium solani are used. Brine shrimps and potato dics are used for anticancer and antitumor potency of extract. High performance liquid chromatography (HPLC) is utilized for determination of bioactive metabolites responsible for the activity. RESULTS: HPLC chromatogram revealed the presence of orientin, isoquercetin, myricetin and apigenin. Various fractions of C. oapca showed significant antibacterial, antitumor and anticancer activity. In case of C. opaca fruit inhibition growth of Aspergillus niger was ranged between 23.2 ± 1.36% to 43.3 ± 2.39%, Aspergillus flavus ranged between 27.6 ± 1.39% to 65.6 ± 3.44%, Aspergillus fumigatus ranged between 13.2 ± 1.00% to 52.4 ± 1.54% and Fusarium solani ranged between 10.5 ± 1.02% to 14.6 ± 1.74%. CONCLUSION: It can be concluded that, various fractions of C.opaca are accessible source of ethno pharmacy as they are consumed in different areas of Pakistan with ultimate health compensations.