Molecular Screening of Bioactive Compounds of Garlic for Therapeutic Effects against COVID-19.

An outbreak of pneumonia occurred on December 2019 in Wuhan, China, which caused a serious public health emergency by spreading around the globe. Globally, natural products are being focused on more than synthetic ones. So, keeping that in view, the current study was conducted to discover potential antiviral compounds from Allium sativum. Twenty-five phytocompounds of this plant were selected from the literature and databases including 3-(Allylsulphinyl)-L-alanine, Allicin, Diallyl sulfide, Diallyl disulfide, Diallyl trisulfide, Glutathione, L-Cysteine, S-allyl-mercapto-glutathione, Quercetin, Myricetin, Thiocysteine, Gamma-glutamyl-Lcysteine, Gamma-glutamylallyl-cysteine, Fructan, Lauricacid, Linoleicacid, Allixin, Ajoene, Diazinon Kaempferol, Levamisole, Caffeicacid, Ethyl linoleate, Scutellarein, and S-allylcysteine methyl-ester. Virtual screening of these selected ligands was carried out against drug target 3CL protease by CB-dock. Pharmacokinetic and pharmacodynamic properties defined the final destiny of compounds as drug or non-drug molecules. The best five compounds screened were Allicin, Diallyl Sulfide, Diallyl Disulfide, Diallyl Trisulfide, Ajoene, and Levamisole, which showed themselves as hit compounds. Further refining by screening filters represented Levamisole as a lead compound. All the interaction visualization analysis studies were performed using the PyMol molecular visualization tool and LigPlot+. Conclusively, Levamisole was screened as a likely antiviral compound which might be a drug candidate to treat SARS-CoV-2 in the future. Nevertheless, further research needs to be carried out to study their potential medicinal use.

Reversal of cisplatin triggered neurotoxicity by Acacia hydaspica ethyl acetate fraction via regulating brain acetylcholinesterase activity, DNA damage, and pro-inflammatory cytokines in the rodent model.

BACKGROUND: Cisplatin (CisPT) is a chemotherapeutic that outcome in adverse effects including neurotoxicity. We examined the efficacy of hydaspica ethyl acetate extract (AHE) against CisPT-prompted neurotoxicity. METHODS: Group I: Distilled water; Group II: CisPT (12 mg/kg b.w. i.p) on the 13th day of treatment. Group III: received AHE (400 mg/kg b.w) orally for 16 days. Group IV and V received 200 and 400 mg/kg b.w AHE orally for 16 days while CisPT injection on day 13, respectively. Group VI: received Silymarin (100 mg/kg b.w) orally for 16 days and CP (12 mg/kg b.w., i.p.) on day 13. TNF-α, IL6, brain acetylcholinesterase activity (AChE), oxidative trauma markers, genotoxicity, antioxidant enzymes, and morphological alterations in cerebral hemispheres were inspected. RESULTS: AHE administration before CisPT considerably reduced both tissue TNF-α and IL 6 expressions compared to CisPT treated group in a dose-dependent manner. AHE treatment (400 mg/kg b.w) significantly ameliorated brain AChE activity. Brain tissue MDA, H2O2, and NO content were markedly (p < 0.001) elevated after CisPT inoculation while a noticeable (p < 0.001) diminution was observed in AHE treatment groups. AHE treatment significantly (p < 0.001) improved brain antioxidant defense in a dose-dependent manner. Furthermore, AHE efficiently recused CisPT to induce DNA damage in brain tissue as revealed by ladder assay and DNA fragmentation patterns. Histopathological findings revealed severe neurodegenerations in CisPT treated group, however, AHE treatment noticeably precluded morphological alterations and neuron damages induced by CisPT. CONCLUSION: A. hydaspica AHE extract may be provided as a prospective adjuvant that precludes CisPT-induced neurotoxicity due to its radical scavenging and antioxidant potential.

Acacia hydaspica R. Parker ethyl-acetate extract abrogates cisplatin-induced nephrotoxicity by targeting ROS and inflammatory cytokines.

Cisplatin (CisPT) is a chemotherapeutic drug that outcomes in adverse effects. In this study, we examined the effect of A. hydaspica ethyl acetate extract (AHE) in an animal model of cisplatin-induced acute kidney injury (AKI). 36 male Sprague Dawley rats were used in the AKI rat model, and CisPT (7.5 mg/kg BW, i.p) single dose was given. In the pretreatment module, AHE (400 mg/kgBW/day, p.o) was given for 7 days before and after CisPT injection. While in the post-treatment group AHE was administered for 7 days after a single CisPT shot. The standard group received silymarin (100 mg/kg BW, p.o) for 7 days before and after CisPT injection. In HCT 116 tumor xenografts (n = 32) two groups of mice were pretreated with 400 mg/kg AHE orally for 7 days and two groups were treated with distilled water. On day 7 of pretreatment one distilled water and one AHE pretreated group were injected i.p with 15 mg/kg bw dose followed by another dose of CisPT 2 wk later. AHE groups were additionally treated with 400 mg/kg AHE for 3 days/week for 2 weeks. CisPT significantly deteriorated renal function parameters, i.e., PH, specific gravity, total protein, albumin, urea, creatinine, uric acid, globulin and blood urea nitrogen. CisPT treatment increased oxidative stress markers, while lower renal antioxidant enzymes. AHE pretreatment ameliorates significantly (p < 0.0001) CisPT-induced alterations in serum and urine markers for kidney function. Furthermore, AHE pretreatment more efficiently (p < 0.001) decreases oxidative stress markers, attenuate NF-κB, and IL-6 protein and mRNA expression by augmenting antioxidant enzyme levels compared to post-treatment. The histological observations verified the protective effect of AHE. In tumor xenograft mice, AHE treatment significantly reduced CisPT induced oxidative stress while it did not interfere with the anticancer efficacy of cisplatin as shown by significance (p < 0.001) decrease in tumor size after treatment. A. hydaspica AHE might provide a prospective adjuvant that precludes CisPT-induced nephrotoxicity without compromising its antitumor potential.

Tissue microarray profiling and integrative proteomics indicate the modulatory potential of Maytenus royleanus in inhibition of overexpressed TPD52 in prostate cancers.

Maytenus roylanus (MEM) is a plant with anti-proliferative effects against prostate cancer. We aimed to explore the mechanism of action of MEM in prostate cancer (PCa) by employing an in vitro global proteome approach to get useful information of various signaling pathways and effected genes to define the mechanism of MEM action in prostate cancer. We conducted a global proteome analysis of CWR22Rv1after treatment with methanolic extract of MEM. The result of the proteomic profiling of in vitro PCa cells demonstrated the reduction in tumor protein D52 (TPD52) expression after treatment with methanolic extract of MEM. Down-regulation of TPD52 expression at mRNA level was observed by MEM treatment in CWR22Rν1 and C4-2 cells in a dose-dependent fashion probably by cleavage of Caspase 3 and PARP, or by modulation of cyclin-dependent kinases in CWR22Rν1 and C4-2 cells. The progressive character of the TRAMP model demonstrates a chance to evaluate the potential of chemo-preventive agents for both initial and late stages of prostate cancer development, and induction in TPD52 protein expression with development as well as the progression of prostate cancer was observed in the TRAMP model. Analyses of the tissue microarray collection of 25 specimens confirmed the clinical significance of our findings identifying TPD52 as a potential marker for PCa progression. We determined that knockdown of TPD52 (CWR22Rν1 cells), a considerable downregulation was seen at the protein level. Downregulation of TPD52 inhibited the migration and invasive behavior of prostate cancer cells as observed. Moreover, we observed that the siRNA-TPD52 transfection of CWR22Rν1 cells resulted in tumor growth inhibition with a marked reduction in the secretion of prostate-specific antigen (PSA) in the serum. Intraperitoneal injection of MEM considerably slowed tumor growth in athymic mice, inhibited TPD52 expression, and caused a marked reduction in PSA levels of serum as demonstrated by immunoblot screening and immune-histochemical staining. This report illustrates a molecular overview of pathological processes in PCa, indicating possible new disease biomarkers and therapeutic targets.

Microwave-Assisted Rapid Green Synthesis of Gold Nanoparticles Using Seed Extract of Trachyspermum ammi: ROS Mediated Biofilm Inhibition and Anticancer Activity.

Green synthesis of metal nanoparticles using plant extracts as capping and reducing agents for the biomedical applications has received considerable attention. Moreover, emergence and spread of multidrug resistance among bacterial pathogens has become a major health concern and lookout for novel alternative effective drugs has gained momentum. In current study, we synthesized gold nanoparticles using the seed extract of Trachyspermum ammi (TA-AuNPs), assessed its efficacy against drug resistant biofilms of Listeria monocytogenes and Serratia marcescens, and evaluated its anticancer potential against HepG2 cancer cell lines. Microwave-assisted green synthesis of gold nanoparticles was carried out and characterization was done using UV-vis spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Most nanoparticles were observed as spherical and spheroidal with few anisotropies with an average crystalline size of 16.63 nm. Synthesized TA-AuNPs demonstrated significant biofilm inhibitory activity against L. monocytogenes (73%) as well as S. marcescens (81%). Exopolysaccharide (EPS), motility, and CSH, key elements that facilitate the formation and maintenance of biofilm were also inhibited significantly at the tested sub-minimum inhibitory concentrations (sub-MICs). Further, TA-AuNPs effectively obliterated preformed mature biofilms of S. marcescens and L. monocytogenes by 64% and 58%, respectively. Induction of intracellular ROS production in TA-AuNPs treated bacterial cells could be the plausible mechanism for the reduced biofilm formation in test pathogens. Administration of TA-AuNPs resulted in the arrest of cellular proliferation in a concentration-dependent manner. TA-AuNPs decrease the intracellular GSH in HepG2 cancer cell lines, cells become more prone to ROS generation, hence induce apoptosis. Thus, this work proposes a new eco-friendly and rapid approach for fabricating NPs which can be exploited for multifarious biomedical applications.

Phytochemical analysis and Evaluation of hepatoprotective effect of Maytenus royleanus leaves extract against anti-tuberculosis drug induced liver injury in mice.

BACKGROUND: Myrin®-p Forte is an anti-tuberclosis agent that can cause hepatic injuries in clinical settings. Maytenus royleanus (Celastraceae) is a medicinal plant, possesses antioxidant and anticancer activities. The hepatoprotective effect of the methanol extract of Maytenus royleanus leaves (MEM) against Myrin®-p Forte induced hepatotoxicity in mice was investigated. METHODS: Mice were randomly parted into six groups (n = 6). Fixed-dose combination of Myrin®-p Forte (13.5 mg/kg Rifampicin, 6.75 mg/kg Isoniazid, 36.0 mg/kg Pyrazinamide and 24.8 mg/kg Ethambutol; RIPE] was administered for 15 days to induce liver injury. In treatment groups MEM (200 mg/kg and 400 mg/kg doses) and Vitamin B6 (180mg/kg) were administered prior to RIPE. Control group received 2% DMSO. Serum liver function tests, DNA damage, tissue antioxidant enzymes and histopathological alterations were studied. HPLC analysis was performed to determine the chemical composition using standard compounds. RESULTS: The quercitin, gallic acid, luteolin, viteixin, apigenin, kaempherol, hyperoside and myricetin contents of all samples were determined by reverse-phase HPLC. Quercetin (0.217 mg/g dry weight) and luteolin (0.141 mg/g dry weight) were the major flavonoids identified in MEM. Myrin®-p Forte markedly (p < 0.05) deteriorated lipid profile and upregulated the concentration of LDH, AST, ALP, ALT and γ-GT in serum along with DNA fragmentation (37.13 ± 0.47%) and histopathological injuries in hepatic tissues of mice compared with the control group. Myrin®-p Forte increased (p < 0.001) lipid peroxidation and H2O2 while decreased (p < 0.001) the activity level of CAT, SOD, POD, GPx, GST, GSR, γ-GT and GSH. Co-administration of MEM (200 mg/kg; 400 mg/kg) or the vitamin B6 (180 mg/kg) to Myrin®-p Forte administered mice significantly ameliorated LDL, cholesterol, HDL and triglyceride content. Furthermore, MEM dose dependently corrected serum liver function tests, decrease % DNA fragmentation (17.82 ± 0.35 and 7.21 ± 0.32 respectively), DNA damage. MEM treated protect RIPE induced oxidative damage by enhancing antioxidants to oxidants balance. Histological examination comprehends biochemical findings. CONCLUSION: The antioxidant effects of MEM exerted the hepatoprotective potential against the Myrin®-p Forte induced hepatotoxicity in mice.

Ameliorating potency of Chenopodium album Linn. and vitamin C against mercuric chloride-induced oxidative stress in testes of Sprague Dawley rats.

BACKGROUND: Mercury has been documented as an industrial risk that posed a serious danger to human health. Mercury exposure results in oxidative stress that may lead to the pathogenesis of male reproductive dysfunction. The present study investigated the ameliorating potential of Chenopodium album L. and vitamin C against mercuric chloride-induced oxidative deterioration of reproductive functions in adult male rats. METHODS: Group 1 (control) received saline. Group 2 received Mercury (0.15 mg/kg b.w, i.p) dissolved in distilled water. Groups 3 and 4 were given oral gavage of vitamin C (200 mg/kg b.w) and the ethanolic extract of C. album (200 mg/kg b.w) respectively, along with Mercury (0.15 mg/kg b.w, i.p). Group 5 was treated only with C. album (200 mg/kg b.w). After 30 days of the treatment, the rats were dissected and their testicular tissue and the cauda epididymis were used for biochemical analysis while blood plasma was used for protein determination. RESULTS: The applied dose-treatment of Mercury-induced oxidative stress in the testis and cauda epididymis tissues of the rats was apparent by a noteworthy decrease in total protein, CAT, SOD, POD, and GST values while there was increase in ROS and TBARS levels. Furthermore, Mercury decreases daily sperm production and enhanced sperm DNA damage as noticeable by an increase in the head and tail length of comets and decrease in intact DNA. There was no significant effect on the body weight and the weight of the reproductive tissues. Treatment with C. album significantly ameliorated the total protein, ROS, and TBARS content. Similarly, the level of CAT, SOD, POD, and GST was significantly improved and the daily sperm production was significantly increased. Furthermore, C. album administration significantly protected Mercury-induced sperm DNA damage. The results of the extract treatment group were compared with those of vitamin C in detoxifying the oxidative stress and restoring the sperm parameters. CONCLUSION: C. album showed protection against Mercury-induced oxidative stress by ameliorating antioxidant enzyme activity, daily sperm production, and DNA damage in rat testes. This suggests that C. album could be beneficial against toxicity induced by an environmental toxicant.

Correction to: Acacia hydaspica R. Parker ameliorates cisplatin induced oxidative stress, DNA damage and morphological alterations in rat pulmonary tissue.

Following publication of the original article [1], the author reported that Tables 3 and 4 were incorrect due to a production error.

Evaluating the protective potency of Acacia hydaspica R. Parker on histological and biochemical changes induced by Cisplatin in the cardiac tissue of rats.

BACKGROUND: Increase oxidative trauma is the main cause behind Cisplatin (CP) induced cardiotoxicity which restricts its clinical application as anti-neoplastic prescription. Acacia hydaspica is a natural shrub with diverse bioactivities. Acacia hydaspica ethyl acetate extract (AHE) ameliorated drug-induced cardiotoxicity in animals with anti-oxidative mechanisms. Current study aimed to evaluate the protective potential of A. hydaspica against cisplatin-induced myocardial injury. METHODS: Rats were indiscriminately distributed into six groups (n = 6). Group 1: control; Groups 2: Injected with CP (7.5 mg/kg bw, i.p, single dose) on day 16; Group 3: Treated for 21 days with AHE (400 mg/kg b.w, oral); Group 4: Received CP injection on day 16 and treated with AHE for 5 days post injection; Group 5: Received AHE (400 mg/kg b.w/day, p.o.) for 21 days and CP (7.5 mg/kg b.w., i.p.) on day 16; Group 6: Treated with silymarin (100 mg/kg b.w., p.o.) after 1 day interval for 21 days and CP injection (7.5 mg/kg b.w., i.p.) on day 16. On 22nd day, the animals were sacrificed and their heart tissues were removed. Cisplatin induced cardiac toxicity and the influence of AHE were evaluated by examination of serum cardiac function markers, cardiac tissue antioxidant enzymes, oxidative stress markers and histology. RESULTS: CP inoculation considerably altered cardiac function biomarkers in serum and diminished the antioxidant enzymes levels, while increased oxidative stress biomarkers in cardiac tissues AHE treatment attenuated CP-induced deteriorations in creatine kinase (CK), Creatine kinase isoenzymes MB (CK-MB), cardiac Troponin I (cTNI) and lactate dehydrogenase (LDH) levels and ameliorated cardiac oxidative stress markers as evidenced by decreasing lipid peroxidation, H2O2 and NO content along with augmentation in phase I and phase II antioxidant enzymes. Additionally, CP inoculation also induced morphological alterations which were ameliorated by AHE. In pretreatment group more significant protection was observed compared to post-treatment group indicating preventive potential of AHE. The protective potency of AHE was comparable to silymarin. CONCLUSION: Results demonstrate that AHE attenuated CP induce cardiotoxicity. The polyphenolic metabolites and antioxidant properties of AHE might be responsible for its protective influence.

Effect of Acacia hydaspica R. Parker extract on lipid peroxidation, antioxidant status, liver function test and histopathology in doxorubicin treated rats.

BACKGROUND: Doxorubicin (DOX) is an anthracycline agent mostly prescribed for various cancers. However, its treatment is contiguous with toxic effects. Acacia hydaspica prevented drug-induced hepatic-toxicity in animals with anti-oxidative mechanisms. We intended to study the efficacy of A. hydaspica ethyl acetate extract (AHE) for inhibiting DOX- induced liver damage. METHODS: Normal control group received saline; Drug control group received 3 mg/kg b.w. dose of DOX for 6 weeks (single dose/week, intraperitoneal injection) to study the effect of chronic DOX treatment. In co-treatment groups, 200 and 400 mg/kg b.w AHE was given orally for 6 weeks in concomitant with DOX (3 mg/kg b.w, i.p. injection per week). The standard drug group received silyamrin 100 mg/kg b.w (2 doses/week: 12 doses/6 weeks) in conjunction with DOX (single dose/week). Lipid profile, liver function tests (LFTs), antioxidant enzymes, oxidative stress enzymes and morphological alterations were studied to evaluate the hepatoprotective potential of AHE. RESULTS: DOX treatment inhibits body weight gain and upturn liver index. DOX considerably upset serum cholesterol, triglycerides and LDL concentration. On the contrary, it reduced serum HDL amount. DOX induced marked depreciation in serum LFTs, diminish hepatic antioxidant enzymes; however, raised tissue oxidative stress markers accompanied by morphological damages. Co-treatment with AHE dose dependently adjusted DOX-prompted fluctuations in lipid profile, AST, ALP, ALT, total bilirubin, and direct bilirubin concentrations and hepatic weight. Likewise, AHE usage enhanced total protein and hepatic tissue antioxidant enzyme quantities whereas declined oxidative stress markers in hepatic tissue. Correspondingly histopathological examinations aid the biochemical results. The influence of AHE 400 mg/kg b.w dose is analogous to silymarin. CONCLUSION: Acacia hydaspica possibly serve as adjuvant therapy that hampers DOX inveigled liver damage due to the underlying antioxidant mechanism of secondary metabolites.

Acacia hydaspica R. Parker ameliorates cisplatin induced oxidative stress, DNA damage and morphological alterations in rat pulmonary tissue.

BACKGROUND: Cisplatin (CP) drug is platinum compounds used for the treatment of various human malignancies. However, adverse outcomes related to CP restrict its usage. Acacia hydaspica is a natural shrub with various pharmacological properties. The current investigation aimed to assess the protective potential of A. hydaspica polyphenol rich ethyl acetate extract (AHE) against cisplatin (CP) induced pulmonary toxicity. METHODS: Rats were divided into six groups. Group 1 served as control (saline); Group 2 (drug control) recieved single dose of CP (7.5 mg/kg i.p.) on 1st day; Group 3 (extract control) (400 mg/kg bw, p.o.) received AHE for one week; Group 4 (Post-treated) and Group 5 (pretreated) received AHE (400 mg/kg bw/day, p.o) for 7 days after and before CP (7.5 mg/kg b.w., i.p.) respectively; Group 6 (Standard control) received silymarin (100 mg/kg b.w/7 days) before CP. At the end of dosing rats were sacrificed and pulmonary tissue samples were processed for the evaluation of antioxidant enzymes, oxidative stress markers, genotoxicity and histopathological alterations. RESULTS: CP caused body weights loss and increase pulmonary tissue weight. The CP significantly increases oxidative stress markers and decreases tissue antioxidant enzyme levels. Furthermore, CP induced deleterious changes in the microanatomy of pulmonary tissue by rupturing the alveolar septa, thickening of alveolar walls, and injuring the cells with subsequent collapse of blood vessels. AHE pretreatment returned MDA, NO, H2O2 production and improved tissue antioxidant enzyme levels to near normalcy. The histological observations evidenced that AHE effectively rescues the lungs from CP-mediated oxidative damage. CP induction in rats also caused DNA fragmentation which was restored by AHE treatment. Our results suggest that pretreatment more significantly improve CP induced deleterious effects compared with post treatment indicating protective effect. Potency of AHE pretreatment is similar to silymarin. CONCLUSION: These findings demonstrated that A. hydaspica AHE extract might serve as potential adjuvant that prevents CP persuaded pulmonary toxicity due to its intrinsic antioxidant potential and polyphenolic constituents.

Effects of dietary supplements on selected hematological and biochemical parameters of Pakistani athletes.

BACKGROUND: CDC's (Centers for Disease Control and Prevention) National Center for Health statistics recent reports have shown that an upsurge has occurred in the use of dietary supplements among age of 20 years since 1994 and this use shown regular increase. The purpose of our study was to investigate the effect of supplements on the reproductive health on male athletes in Pakistan. METHODS: A total of 150 adult male with mean age of 25.78 ± 0.56 years were included in this study and divided into four groups: Non-athlete control (n = 57), Non supplemental athlete control (n = 40), Supplemental athlete group I (n = 28) and supplemental athlete group II (n = 25). Blood (10 ml) was taken from each subject. Complete blood count was performed and 5 ml of blood was centrifuged to separate plasma and then analyzed for antioxidant enzyme (CAT, POD, GR and GSH) activities, Lipid peroxidation (TBARS), electrolyte, metal (sodium, potassium and zinc) and Luteinizing hormone (LH) concentration. RESULTS: Complete blood count results showed normal RBC, WBC, Platelets, Hemoglobin, Hematocrit, Mean corpuscular hemoglobin and Mean corpuscular hemoglobin concentration. Antioxidant enzymes (CAT, POD, GR, GSH) increased significantly in supplemental athletes as compared to control groups. Sodium and potassium showed significant increase (p < 0.001) in supplemental athlete group I, while TBARS also showed significant increase (p < 0.05) in supplemental group I and II as compared to non athlete control while non supplemental athletes showed significant increase (p < 0.05) in TBARS concentration as compared to non athlete control. LH concentration was found to be decreased significantly (p < 0.05) in supplemental group I and II as compared to control groups. CONCLUSION: It is therefore concluded from the present results that oxidative stress was considerably elevated in response to supplement consumption among athletes which may affect their health haematological parameters and reproductive hormones.

Acacia hydaspica ethyl acetate extract protects against cisplatin-induced DNA damage, oxidative stress and testicular injuries in adult male rats.

BACKGROUND: Cisplatin (CP), an effective anticancer agent, carries the risk of impairing testicular function leading to infertility. The present study aimed at evaluating the protective effect of A. hydaspica ethyl acetate extract (AHE) against CP-induced oxidative stress and testicular injuries in rats. METHODS: Rats were divided into six groups (n = 6). Group I (control), group II (CP single dose on day 16). Group III received AHE for 21 days. Group IV (CP + AHE; post- treatment group). Group V (AHE + CP; pre-treatment group) and group VI (CP + Sily). RESULTS: CP treatment reduced serum testosterone (T), LH and FSH, decreased the activity level of antioxidant enzymes while increased the concentration of oxidative stress markers, i.e. thiobarbituric acid reactive substances (TBARS), H2O2 and nitric oxide (NO) along with corresponding DNA damages. Furthermore, CP induced adverse morphological changes in testis of rats including reduced epithelial height and tubular diameter, increased luminal diameter with impaired spermatogenesis. Pre and post-treatment with AHE reduced the side effects of CP in testis tissues through improvement in the reproductive hormonal secretions, enzymatic activities, histological and DNA damage parameters. Pretreatment seems to be more effective and equivalent to silymarin group in reversing the CP deleterious effects as compared to post-treatment. CONCLUSION: The results demonstrated that A. hydaspica treatment in CP-induced testicular toxicity augments the antioxidants defense mechanism, reverted the level of fertility hormones, suppressed the histomorphological alterations and DNA damages and thus provides the evidence that it may have a therapeutic role in free radical mediated diseases.

Acacia hydaspica R. Parker prevents doxorubicin-induced cardiac injury by attenuation of oxidative stress and structural Cardiomyocyte alterations in rats.

BACKGROUND: The use of doxorubicin (DOX) an anthracycline antineoplastic agent is withdrawn due to its cardio-toxic side effects. Oxidative stress has been recognized as the primary cause of DOX induced cardiotoxicity. We have investigated whether polyphenol rich ethyl acetate extract of Acacia hydaspica (AHE) can attenuate doxorubicin-induced cardiotoxicity via inhibition of oxidative stress. METHODS: AHE was administered orally to rats once daily for 6 weeks at doses of 200 and 400 mg/kg b.w. DOX (3 mg/kg b.w. i.p., single dose/week) was administered for 6 weeks (chronic model). The parameters studied to evaluate cardioprotective potential were the serum cardiac function biomarkers (CK, CKMB, AST and LDH), hematological parameters, cardiac tissue antioxidant enzymatic status and oxidative stress markers, and histopathological analysis to validate biochemical findings. RESULTS: Chronic 6 week treatment of DOX significantly deteriorated cardiac function biomarkers and decreased the activities of antioxidant enzymes, whereas significant increase in oxidative stress biomarkers was noticed in comparison to control group. AHE dose dependently protected DOX-induced leakage of cardiac enzymes in serum and ameliorated DOX-induced oxidative stress; as evidenced by decreasing lipid peroxidation, H2O2 and NO content with increase in phase I and phase II antioxidant enzymes. Doxorubicin treatment produced severe morphological lesions, leucopenia, decrease in red blood cell counts and hemoglobin concentrations. AHE co-treatment protected the heart and blood elements from the toxic effects of doxorubicin as indicated by the recovery of hematological parameters to normal values and prevention of myocardial injuries in a dose dependent way. The protective potency of AHE (400 mg/kg b.w) was equivalent to silymarin. CONCLUSION: Results revealed that AHE showed protective effects against DOX induce cardiotoxicity. The protective effect might attribute to its polyphenolic constituents and antioxidant properties. AHE might be helpful in combination therapies as safer and efficient.

Modulatory influence of Acacia hydaspica R. Parker ethyl acetate extract against cisplatin inveigled hepatic injury and dyslipidemia in rats.

BACKGROUND: Cisplatin (CP) is recommended as a first-line chemotherapeutic agent for solid tumors, however its usage outcomes in severe adverse effects. Acacia hydaspica possesses various phytochemicals and pharmacological activities. The current study aimed to investigate the protective effect of A. hydaspica ethyl acetate extract (AHE) against CP induced aberrations in lipid profile and hepatotoxicity. METHODS: Rats were randomly separated into six groups (n = 6). Group 1 (control) received distilled water orally for 21 days. Groups 2 (CP control) received a single dose of CP (7.5 mg/kg bw, i.p) on day 16, group 3 (Plant control) received AHE (400 mg/kg b.w, oral) for 21 days, group 4 (post treated group); CP received on day 16 and AHE (400 mg/kg b.w/day, p.o.) was administered after CP till day 21, Group 5 (pretreated group) received AHE (400 mg/kg b.w/day, p.o.) for 21 days and CP (7.5 mg/kg b.w., i.p.) on day 16, group 6 (Silymarin + CP) received 100 mg/kg b.w., p.o. (11 doses/21 days) and CP (7.5 mg/kg b.w., i.p.) on day 16. Lipid profile, liver functional tests, oxidative stress markers, antioxidant enzymes status and histopathological changes were examined. RESULTS: The present study revealed that CP caused body weights loss and increase liver index. CP significantly increased serum total lipid, triglycerides and LDL-cholesterol levels. Conversely, it significantly decreased serum HDL-cholesterol level. CP induced marked deteriorations in serum liver function biomarkers, reduced antioxidant enzymes in tissue, while elevated tissue oxidative stress markers along with morphological injuries compared to control rats. Treatment with AHE ameliorated CP induced alterations in lipid profile, serum ALT, AST, ALP and total bilirubin levels and liver weight. Furthermore AHE treatment improved the total protein and antioxidant enzymes levels while decreased the level of MDA, H2O2, and NO. The altered parameters were returned to the control level with AHE pretreatment. Histopathological analysis also supported the biochemical findings. Pretreatment seems to be more effective compared to post treatment indicating protective effect. CONCLUSION: These results reveal that treatment of AHE may be useful in the prevention of CP induced hepatotoxicity due to its antioxidant potential and polyphenolic constituents.

Anti-depressant and anxiolytic potential of Acacia hydaspica R. Parker aerial parts extract: Modulation of brain antioxidant enzyme status.

BACKGROUND: Oxidative stress may link to psychiatric disorders, and is being regarded as a plausible mechanism that can affect the regulation of these illnesses. The present study was undertaken to investigate the antidepressant and anxiolytic potential of A. hydaspica R. parkers. Brain oxidative stress enzyme levels were analyzed to correlate depression and stress with brain antioxidant status. METHODS: Antidepressant and anxiolytic effect of methanol extract of A. hydaspica and its derived soluble fractions [n-hexane (AHH), ethyl-acetate (AHE), chloroform (AHC), n-butanol (AHB) and remaining aqueous fraction (AHA)] was investigated by using three behavioral models; the Forced swimming test, Tail suspension test and Elevated plus-maze test (EPM). Chronic unpredictable mild stress (CMS) was employed to induce stress in rats. AHM and AHE (200 mg/kg, p.o), fluoxetine (5 mg/kg, i.p) and diazepam (DZM) (1 mg/kg, p.o) were administered during the 7 day stress exposure period, and rats were assessed for antidepressant and anxiolytic behavioral despair paradigms. Antioxidant enzymes and oxidative stress markers were measured in brain tissue of depressed rats. Phytochemical analysis was done by GCMS experimentation. RESULTS: AHM and AHE (acute dose) significantly (p < 0.0001) reduced the immobility time and ameliorated climbing behavior as compared to the control in FST and TST, and similar to fluoxetine. AHM and AHE showed significant (p < 0.0001) anxiolytic potential in EPM, and comparable to DZM (1 mg/kg b.w., i.p). Significant decrease in antioxidant enzyme levels and increase in MDA, H2O2 and NO level were observed in stressed rats. AHM and AHE (for 7 days/CMS) significantly improved behavior in FST, TST and EPMT. Treatment also improved antioxidant enzyme level and controlled the oxidative stress markers in brain tissues. GCMS analysis indicated the presence of 10 different chemical constituents in A. hydaspica. CONCLUSION: The present study revealed that A. hydaspica exerts an antidepressant and anxiolytic effect by improving brain antioxidant status. The observed activities might be due to the presence of diverse phytochemicals.

Evaluation of antioxidant, anti-hemolytic and anticancer activity of various solvent extracts of Acacia hydaspica R. Parker aerial parts.

BACKGROUND: Acacia hydaspica R. Parker, family leguminosae, is a medicinally important plant. Different plant parts are used in various ailments in folk medicine. The current study aimed at investigating the in vitro antioxidant, anti-hemolytic and anticancer activity of A. hydaspica. METHODS: Antioxidant potential was assessed using DPPH, ABTS and •OH, scavenging of H2O2, inhibition of lipid peroxidation and ß-carotene bleaching inhibition assays. Anti-hemolytic activity was assessed using H2O2 induced hemolysis of RBCs. Anticancer potential was assessed using MTT assay. Spectrometric methods and HPLC-DAD analysis was performed for phytochemical screening. RESULTS: EC50 values based on reduction of DPPH, ABTS and •OH, scavenging of H2O2, inhibition of lipid peroxidation and ß-carotene bleaching for AHB, AHE and AHM were generally lower manifesting potential antiradical capacities. The fractions also exhibited significant (P <0.001) anti-hemolytic potential. Regarding IC50 values for anticancer activity against HCC-38 and MDA-MB-361 cancer cell lines; AHB, AHE and AHM exhibited significant (P <0.001) cyto-selection indices. Plant extracts showed no cytotoxicity against normal Vero cells (IC50 > 250 µg/ml). While significant (P <0.001) cytotoxicity was elicited by these extract/fractions against cancer cell lines. AHE was the most effective and IC50 was found to be 29.9 ± 0.909 µg/ml (SI = 9.83) and 39.5 ± 0.872 µg/ml (SI = 7.44) against MDA-MB-361 and HCC-38 cancer cells respectively. Higher amounts of TPC and TFC were exhibited by AHE and AHB as compared to other fractions. Gallic acid, catechin and myricetin were identified in AHE whereas gallic acid and catechin were identified in AHB by HPLC. CONCLUSION: The presence of bioactive constituents in AHE and AHB might be responsible for antioxidant, anti-hemolytic and anticancer activities.

Antipyretic, anti-inflammatory and analgesic activity of Acacia hydaspica R. Parker and its phytochemical analysis.

BACKGROUND: Inflammation and pain underlies several pathological conditions. Synthetic drugs used for the management of these conditions carry severe toxic effects. Globally efforts are ongoing to introduce novel medicinal plants to develop effective, economic and innocuous drugs. The current study was aimed at investigating the antipyretic, anti-inflammatory and analgesic activity of methanol extract of A. hydaspica aerial parts (AHM) and its active fraction. Furthermore identification and isolation of polyphenolic compounds was carried out to identify the active principles. METHODS: Yeast induced pyrexia, Paw edema, acetic acid-induced writhing and hot plate test were carried out in vivo. HPLC-DAD analysis and combination of different chromatographic techniques, involving vacuum liquid chromatography (VLC) and flash chromatography (FC) were carried out for chemical characterization. The structural heterogeneity of flavanols was characterized by ESI- MS, (1)H NMR, (13)C NMR and (2)D NMR spectroscopic analyses, and also by comparison with reported literature. RESULTS: Oral administration of A. hydaspica methanol extract (AHM) and A. hydaspica ethyl acetate fraction (AHE), showed dose and time dependent decrease in body temperature in yeast induced pyrexia, comparable to standard, Paracetamol. AHM and AHE (150 mg/kg) significantly (p < 0.001) inhibit pain sensation in various pain models, i.e. acetic acid induced writhing and hot plate test. Similarly AHM and AHE demonstrated an anti-inflammatory effect in carrageenan-induced paw edema in rats and 150 mg/kg dose being distinctly more effective (91.92% inhibition). When studied on prostaglandin E2 (PGE2) induced edema in rats, AHM and AHE showed maximum inhibition of edema at 150 mg/kg after 4 h. HPLC chromatogram of AHM revealed the presence of gallic acid, catechin, rutin and caffeic acid. Chromatographic separation and structure characterization of AHE, has led to the identification of three flavan-3-ol derivative including 7-O-galloyl catechin, +catechin and methyl gallate, which have been reported for the first time in A. hydaspica. CONCLUSION: These results revealed that the presence of bioactive compounds in A. hydaspica might be responsible for the pharmacological activities, confirming the indigenous utility of A. hydaspica against inflammatory disorders.