Jasminum humile (Linn) ameliorates CCl4-induced oxidative stress by regulating ER stress, inflammatory, and fibrosis markers in rats.

Jasminum humile (Linn) is highly valued for its medicinal properties. The pulp and decoction made from its leaves are effective for skin diseases. Juice prepared from roots is used against ringworm illness. Our current study aims to illustrate the non-toxicity and protective potential of methanol extract of Jasminum humile (JHM) against CCl4-induced oxidative stress in the liver of rats. Qualitative phytochemical screening, total flavonoids (TFC), and total phenolic content (TPC) assays were performed with JHM. The toxicity of the plant was estimated by treating female rats at different JHM doses while to assess anti-inflammatory potential of plant nine groups of male rats (six rats/group) received different treatments such as: CCl4 only (1 ml/kg mixed with olive oil in a ratio of 3:7), silymarin (200 mg/kg) + CCl4, different doses of JHM alone at a ratio of 1:2:4, and JHM (at a ratio of 1:2:4) + CCl4, and were examined for different antioxidant enzymes, serum markers, and histological changes, while mRNA expression of stress, inflammatory and fibrosis markers were assessed by real-time polymerase chain reaction analysis. Different phytochemicals were found in JHM. A high amount of total phenolic and flavonoid content was found (89.71 ± 2.79 mg RE/g and 124.77 ± 2.41 mg GAE/g) in the methanolic extract of the plant. Non-toxicity of JHM was revealed even at higher doses of JHM. Normal levels of serum markers in blood serum and antioxidant enzymes in tissue homogenates were found after co-administration of JHM along with CCl4. However, CCl4 treatment caused oxidative stress in the liver by enhancing the levels of stress and inflammatory markers and reducing antioxidant enzyme levels, while JHM treatment showed significant (P < 0.05) downregulation was in mRNA expression of those markers. Investigation of mechanism of specific signaling pathways related to apoptosis and clinical trials to assess safety and efficacy of optimal dosage of Jasminum humile will be helpful to develop FDA-approved drug.

Linum corymbulosum Protects Rats against CCl4-Induced Hepatic Injuries through Modulation of an Unfolded Protein Response Pathway and Pro-Inflammatory Intermediates.

Liver fibrosis is a major pathological feature of chronic liver disease and effective therapies are limited at present. The present study focuses on the hepatoprotective potential of L. corymbulosum against carbon tetrachloride (CCl4)-induced liver damage in rats. Analysis of Linum corymbulosum methanol extract (LCM) using high-performance liquid chromatography (HPLC) revealed the presence of rutin, apigenin, catechin, caffeic acid and myricetin. CCl4 administration lowered (p < 0.01) the activities of antioxidant enzymes and reduced glutathione (GSH) content as well as soluble proteins, whereas the concentration of H2O2, nitrite and thiobarbituric acid reactive substances was higher in hepatic samples. In serum, the level of hepatic markers and total bilirubin was elevated followed by CCl4 administration. The expression of glucose-regulated protein (GRP78), x-box binding protein-1 total (XBP-1 t), x-box binding protein-1 spliced (XBP-1 s), x-box binding protein-1 unspliced (XBP-1 u) and glutamate-cysteine ligase catalytic subunit (GCLC) was enhanced in CCl4-administered rats. Similarly, the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemo attractant protein-1 (MCP-1) was strongly increased with CCl4 administration to rats. Co-administration of LCM along with CCl4 to rats lowered (p < 0.05) the expression of the above genes. Histopathology of the liver showed hepatocyte injury, leukocyte infiltration and damaged central lobules in CCl4-treated rats. However, LCM administration to CCl4-intoxicated rats restored the altered parameters towards the levels of control rats. These outcomes indicate the existence of antioxidant and anti-inflammatory constituents in the methanol extract of L. corymbulosum.

Evaluation of Phytochemistry and Pharmacological Properties of Alnus nitida.

In the current study, the anti-inflammatory and analgesic potential of Alnus nitida (leaves and fruits) was evaluated in the Sprague-Dawley rat. Traditionally, A. nitida was used for the treatment of inflammatory ailments. However, A. nitida leaves and fruits have not been yet reported regarding any potential medicinal effects. Leaves/fruits of A. nitida were extracted with methanol and fractionated to attain n-hexane, chloroform, ethyl acetate and aqueous fractions. These extracts were then evaluated for in vivo analgesic and anti-inflammatory potential. For in vivo anti-inflammatory activity, carrageenan-induced paw edema assay, Freunds' complete adjuvant-induced edema, xylene-induced ear edema and histamine-induced paw edema models were used in rats, which showed significant (p < 0.01) reduction (70−80%) in edema in comparison of inflammatory controls. On other hand, for the analgesic assessment, hot plate assay and acetic acid-induced writhing tests were used, which showed a significant (p < 0.01) rise in latency time (40−60%) as compared with pain-induced controls. These results were comparable with standard drugs in a concentration-dependent manner and no mortality or toxicity was observed during all experiments. Then, for the identification of chemical constituents gas chromatography−mass spectrometry (GC-MS) analysis was performed, which indicated the presence of neophytadiene, 3,7,11,15-Tetramethyl-2-hexadecen-1-ol, phytol and vitamin E, justifying the use of A. nitida to treat inflammatory disorders.

In vitro antimicrobial and cytotoxic manifestations of Dicliptera roxburghiana.

Emerging resistance in microorganisms is a growing threat to human beings due to its role in pathological manifestations in different infectious diseases. This study was designed to investigate the antimicrobial and cytotoxic potential of methanol extract of Dicliptera roxburghiana and all its derived fractions. Antibacterial (against six bacterial strains) and antifungal (against four fungal strains) activities were investigated by agar well diffusion method and agar slants method, respectively. Cytotoxicity assay was carried out by using Brine shrimps eggs. In antibacterial evaluation, MIC values and zone of inhibition were measured and were found very effective for DRME, DRHF, DRCF and DREF while these were moderate for DRBF and DRAF. For antifungal assay, DRME and DRHF were potently active and showed more than 70% fungal growth inhibition where as DRCF and DRBF were also displaying appreciable inhibition. Cytotoxic measurements were very good for DRME, DRHF and DRAF with LD50 values 215, 199 and 392µg/ml respectively. These results confirmed antimicrobial and cytotoxic potential of the plant and all its derived fractions. Hence it can be concluded that plant contain some important compounds that can be used as antimicrobial source for the treatment of different infectious disease.

Investigation of Chemopreventive and Antiproliferative Potential of Dicliptera roxburghiana.

CONTEXT: Carcinogenesis causes much human misery. It is a process involving multistage alterations. Medicinal plants are candidates for beneficial anticancer agents. OBJECTIVES: Investigation of anticancer proficiencies of the plant Dicliptera roxburghiana. MATERIAL AND METHODS: Crude extract and derived fractions were inspected for their inhibitory potential against nuclear factor KB (NFκB), nitric oxide synthase inhibition, aromatase inhibition and induction of quinone reductase 1 (QR 1). Antiproliferative activity was determined by using various cancer cell lines for example hormone responsive breast cancer cell line MCF-7, estrogen receptor negative breast cancer cell line MDA-MB-231, murine hepatoma cells Hepa 1c1c7, human neuroblastoma cells SK-N-SH and neuroblastoma cells MYCN-2. RESULTS: Ethyl acetate and n-butanol fractions of D. roxburghiana were strongly active against NFκB with IC50 of 16.6 ± 1.3 and 8.4 ± 0.7 µg/ml respectively with 100% survival. Chloroform fraction of the plant exhibited an induction ratio of 2.4 ± 0.09 with CD value of 17.7 µg/ml. Regarding the nitrite assay, the n-hexane fraction exhibited significant inhibition of NO activity with IC50 of 17.8 ± 1.25 µg/ml. The n-butanol fraction exhibited strong antiproliferative activity against IcIc-7 cell lines with IC50 values of 13.6 ± 1.91 µg/ml; against MYCN-2 a cytotoxic effect developed with dose dependence, with IC50 of 12.6 ± 1.24 µg/ml. In antiproliferative activity against SK-N-SH cell lines, chloroform, ethyl acetate and n-butanol fractions were efficiently active with IC50 values of 11.2 ± 0.84, 14.6 ± 1.71 and 16.3 ± 1.57 respectively. DISCUSSION AND CONCLUSION: It was demonstrated that various fractions of D. roxburghiana displayed appreciable anticancer characteristics and could be a potent source for the development of anticancer leads.

Green synthesized silver nanoparticles (AgNPs) from Parrotiopsis jacquemontiana (Decne) Rehder leaf extract and its biological activities.

Parrotiopsis jacquemontiana (Decne) Rehder aqueous extract of leaf was used for biosynthesis of AgNPs and characterized through UV-Visible spectroscopy, X-ray diffraction, Fourier-transform-infrared, diffraction light scattering, and scanning electron microscope analysis. Moderate to strong antioxidant activity during in vitro antioxidant assays for scavenging of 2,2-diphenyl-1-picryl hydrazyl (DPPH), hydroxyl (OH), nitric oxide (NO) radicals, iron chelation, and inhibition of ß-carotene bleaching was recorded with minimum IC50 value (27.70 ± 2.67 µg/ml) calculated for OH radicals. The AgNPs were evaluated against six multidrug resistant human bacterial strains and minimum inhibitory concentration (MIC) along with minimum bactericidal concentration (MBC) values was determined and all were found remarkably susceptible. The bacterial strain Staphylococcus aureus was the most susceptible with MIC = 5 µg/ml and MBC = 10 µg/ml. Among six fungal strains, Fumigatus esculentum was the most susceptible with MIC and MBC of 10 µg/ml. 3-(4,5-Dimethylthiazol-2 yl)-2,5-diphenyltetrazolium bromide (MTT) screening assay against cancer cell lines (HCCLM3, HEPG2, MDA-MB 231, and MCF-7) revealed the least IC50 values against HCCLM3 (74.20 ± 5.04) and MCF-7 (91.90 ± 1.17). While no cytotoxicity against normal cell lines; LO2 and MCF-10a was recorded. Parrotiopsis jacquemontiana silver nanoparticles (PJAgNPs) significantly (p > .001) prevented the migration of HCCLM3 cells in a dose-dependent style, relative to control. The wound healing potential of AgNPs in rat was found higher (p < .05) for wound contraction rates, hydroxyproline content, hemostatic and re-epithelization and regeneration efficiency in comparison to the reference group.

Indigofera linifolia ameliorated CCl4 induced endoplasmic reticulum stress in liver of rat.

ETHNOPHARMACOLOGICAL RELEVANCE: Indigofera linifolia (L.f.) Retz. is used in subcontinent for liver disorders, in wounds, febrile eruption and as diuretic. AIM OF STUDY: The current study evaluates the protective effects of the methanol extract of Indigofera linifolia (ILM) on CCl4-induced endoplasmic reticulum (ER) stress in liver of rat. METHODS: ILM was analyzed for phytochemical classes, total phenolic (TPC) and flavonoid content (TFC) as well as multidimensional in vitro antioxidant assays. Male (Sprague Dawley) rats were dispersed into seven groups (6 rats/group) receiving 0.9% saline (1 ml/kg bw), CCl4 (1 ml/kg bw) diluted in olive oil (3:7 v/v), silymarin (200 mg/kg bw) + CCl4 (30% v/v), ILM (150 mg/kg bw) + CCl4 (30% v/v), ILM (300 mg/kg bw) + CCl4 and ILM alone (either 150 mg/kg bw or 300 mg/kg bw). RESULTS: ILM extract was constituted of different phytochemical classes. Co-administration of ILM along with CCl4 to rat revert the level of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and total bilirubin in blood serum and antioxidant parameters in liver. Further, CCl4 increased the level of ER stress markers and inflammatory mediators while decreased level of GCLC and Nrf-2 in liver tissues of rat. CCl4-induced histopathological variations were reduced with ILM co-administration in liver tissues. CONCLUSION: The results suggest that active phyto-constituents of I. linifolia might be responsible for its antioxidant, anti-inflammatory and gene-regulating activities.

Characterization and phytochemical constituents of Periploca hydaspidis Falc crude extract and its anticancer activities.

The current study aims to investigate the anticancer potential of Periploca hydaspidis extracts against HCCLM3 and MDA-MB 231 cell lines with invasive properties and to identify molecular targets underlying its action mechanism. Cytotoxic screening of plant extracts was done via MTT assay against liver and breast cancer cell lines and GC/MS of the best cytotoxic fraction was performed to identify its chemical composition. Flow cytometry detected apoptosis and cell-cycle changes after drug treatment. The specified cells were studied for migration and invasion potential along with performing western blot analysis of proteins involved in apoptosis, cell-cycle, metastasis, and MAPK (Mitogen-activated protein kinase) cell-signaling pathway. The results revealed the crude methanol (PHM) fraction of P. hydaspidis shown dose and time dependent cell-proliferative inhibition response. GC/MS analysis detected 54 compounds of which fatty acids (29.8%), benzenoids (15.7%), and esters (14.3%) constituted the bulk. The inhibitory effect against cancer cells was linked with cell-cycle arrest at G0/G1 phase, induction of apoptosis, reduced migration and invasion capabilities post treatment. PHM induced apoptosis via downregulation of anti-apoptotic (survivin, B-cell lymphoma Extra-large; BCL-XL, X-linked inhibitor of apoptosis protein; XIAP, Myelocytomatosis; C-myc), metastatic (Matrix metallopeptidases 9/2; MMP9/2), and cell-cycle regulatory (cyclin D1 and E) proteins, whereas upregulation of pro-apoptotic proteins (Bcl-2 homologous antagonist/killer; BAK, Bcl-2-Associate X protein; BAX, cleaved caspases; 3,7,8,9, and PARP) and activation of MAPK (Jun amino-terminal kinase; JNK and P38) pathway. P38 was needed for PHM-induced apoptosis, where the inhibition of P38 by pharmacological inhibitor (SB239063) diminished the apoptotic effects. Overall, our results conclude that PHM can inhibit cell-proliferation and induce apoptotic effects by activation of P38 MAPK cell-signaling pathway. This suggests the methanol fraction of P. hydaspidis (PHM) to have anticancer compounds, potentially useful for treating liver and breast cancer. In future, one-step advance studies of PHM regarding its role in metastatic inhibition, immune response modulation for reducing tumor, and inducing apoptosis in suitable animal models would be an interesting and promising research area.

In vitro anticancer activity of extracted oil from Parrotiopsis jacquemontiana (Decne) Rehder.

BACKGROUND: Parrotiopsis jacquemontiana, commonly referred to as "Beranj" in the local community, is widely used traditionally and has numerous health benefits. However, no studies have been conducted to investigate its anticancer potential, particularly its extracted oil. PURPOSE: The present study was put forth to appraise the anticancer potential of Parrotiopsis jacquemontiana extracted oil against liver (hcclm3 and hepg2) and breast cancer (mda-mb 231 and mcf-7) cell lines relative to normal cell lines (lo2 and mcf-10a) via MTT assay. METHODS: Flow cytometry indicated the apoptotic effect whereas invasion and migration capabilities of oil against cancer cells were determined by Matrigel invasion chamber and wound-scratch assays. RESULTS: The results of oil revealed a time and dose-dependent increase in cell proliferation inhibition, conferring to least IC50 shown against hcclm3 (144.9 ± 0.75 µg/ml) and mda-mb 231 (145.7 ± 0.32 µg/ml) cell line at 72 h, whereas no cytotoxic effect on normal cells was observed. In addition, the oil significantly (p < 0.001) suppressed the migration and invasion of hcclm3 and mda-mb 231 cells, showing noteworthy anti-metastatic potential. Furthermore, cell death was confirmed by Annexin‒V/PI staining where the maximum apoptotic percentage was calculated for oil (200 µg/ml) alongside mda-mb 231 conferring to 15.36 ± 1.22, 26.7 ± 1.2, and 36.43 ± 1.65 at 24, 48, and 72 h whereas 12.33 ± 1.05, 19.36 ± 1.62, and 29.3 ± 0.79 was recorded alongside hcclm3 at similar time intervals, respectively. CONCLUSION: In conclusion, the extracted oil exhibited strong anti-proliferative, anti-metastatic, and apoptotic effects and therefore may have potential applications in cancer treatment, however, further studies of oil regarding the action mechanisms and compounds involved in anticancer therapy are necessary.

Green synthesized AgNPs from Periploca hydaspidis Falc. and its biological activities.

Characterization of bio-synthesized silver nanoparticles (AgNPs) using Periploca hydaspidis (PHAgNPs) whole plant extract for the first time via UV-Visible spectroscopy, XRD, FTIR, DLS, and SEM analysis techniques was done. A rich variety of phytochemicals in P. hydaspidis aqueous extract (PHA) functioned as possible reducing and capping agents for AgNPs synthesis. In vitro antioxidant activities (DPPH, Iron chelating, Hydroxyl ion, Nitric oxide, and ß-carotene bleaching assays) of PHAgNPs revealed least IC50 values especially in hydroxyl ion (39.08 ± 0.88 µg/mL) and nitric oxide (37.53 ± 2.24 µg/mL) scavenging assays relative to standard controls (ascorbic acid, rutin, and gallic acid) and PHA. In addition, visible inhibition zone diameters were formed around discs against all pathogenic microbial strains including multi-drug resistant strains (MDR's). MIC and MBC/MFC were depicted least in PHAgNPs with maximum bactericidal/fungicidal effects. MTT assay displayed a significant antiproliferative potential of PHAgNPs against HCCLM3, MCF-7, MDA-MB 231, and HEPG2 cancer cell lines, where least IC50 values were recorded against HEPG2 (12.97 ± 0.04 µg/mL) and MCF-7 (5.73 ± 0.22 µg/mL). Furthermore, PHAgNPs considerably (p > 0.001) prevented the migration of MCF-7 cancer cells in vitro whereas in in vivo wound healing assay, faster skin regeneration, and epithelization in wound biopsies was observed via histological analysis. PHAgNPs treated group rats significantly increased (p < 0.05) the wound contraction rate, hydroxyproline content and hemostatic potential compared to control and PHA-treated groups.

Phytochemicals of Periploca aphylla Dcne. ameliorated streptozotocin-induced diabetes in rat.

BACKGROUND: Periploca aphylla is used by local population and indigenous medicine practitioners as stomachic, tonic, antitumor, antiulcer, and for treatment of inflammatory disorders. The aim of this study was to evaluate antidiabetic effect of the extract of P. aphylla and to investigate antioxidant and hypolipidemic activity in streptozotocin (STZ)-induced diabetic rats. METHODS: The present research was conducted to evaluate the antihyperglycemic potential of methanol extract of P. aphylla (PAM) and subfractions n-hexane (PAH), chloroform (PAC), ethyl acetate (PAE), n-butanol (PAB), and aqueous (PAA) in glucose-overloaded hyperglycemic Sprague-Dawley rats. Based on the efficacy, PAB (200 mg/kg and 400 mg/kg) was tested for its antidiabetic activity in STZ-induced diabetic rats. Diabetes was induced via intraperitoneal injection of STZ (55 mg/kg) in rat. Blood glucose values were taken weekly. HPLC-DAD analysis of PAB was carried out for the presence of various polyphenols. RESULTS: HPLC-DAD analysis of PAB recorded the presence of rutin, catechin, caffeic acid, and myricetin. Oral administration of PAB at doses of 200 and 400 mg/kg for 21 days significantly restored (P < 0.01) body weight (%) and relative liver and relative kidney weight of diabetic rats. Diabetic control rats showed significant elevation (P < 0.01) of AST, ALT, ALP, LDH, total cholesterol, triglycerides, LDL, creatinine, total bilirubin, and BUN while reduced (P < 0.01) level of glucose, total protein, albumin, insulin, and HDL in serum. Count of blood cells and hematological parameters were altered in diabetic rats. Further, glutathione peroxidase, catalase, superoxide dismutase, glutathione reductase, and total soluble protein concentration decreased while concentration of thiobarbituric acid reactive substances and percent DNA damages increased (P < 0.01) in liver and renal tissues of diabetic rats. Histopathological damage scores increased in liver and kidney tissues of diabetic rats. Intake of PAB (400 mg/kg) resulted in significant improvement (P < 0.01) of above parameters, and results were comparable to that of standard drug glibenclamide. CONCLUSION: The result suggests the antihyperglycemic, antioxidant, and anti-inflammatory activities of PAB treatment in STZ-compelled diabetic rat. PAB might be used as new therapeutic agent in diabetic patients to manage diabetes and decrease the complications.

Pharmacological evaluation of Acacia modesta bark for antipyretic, anti-inflammatory, analgesic, antidepressant and anticoagulant activities in Sprague Dawley rats.

In this study the bark of Acacia modesta was evaluated for anti-inflammatory, antipyretic, analgesic, antidepressant and anticoagulant activity by carrageenan, hot plat, forced swim and capillary tube method respectively in rats. Highest anti-inflammatory activity was exhibited by chloroform (AMC) extract (74.96% inhibition) while other two active fractions being n-hexane (AMH) and ethyl acetate (AME) exhibited 71.26% and 52.87% inhibition of edema respectively. On the other hand, the aqueous (AMA) fraction showed most effective response with 67.06% analgesic activity. Additionally, the significant (p<0.05) post-treatment antipyretic effect was found by all fractions in time dependent manner. The current findings showed that AMC, AME and AMA had significant reduction in immobility time in the antidepressant test, while AMH showed mild antidepressant activity. In anticoagulant assay, the coagulation time of crude extract A. modesta and its all fractions were comparable to that of positive control aspirin (208s). Moreover, neither mortality nor lethality was observed in the tested animals. Overall, the plant extracts showed potent anti-inflammatory, antipyretic, analgesic, antidepressant and anticoagulant activities which concludes that the bark of A. modesta have significant therapeutic potential.

Gonadoprotective ability of Vincetoxicum arnottianum extract against bisphenol A-induced testicular toxicity and hormonal imbalance in male Sprague Dawley rats.

Vincetoxicum arnottianum (Wight) of family Apocynaceae is a rich source of therapeutic alkaloids, phenolics and flavonoids. Study aims to evaluate the protective potential of methanol extract of Vincetoxicum arnottianum (VAM) on bisphenol A (BPA)-induced testicular toxicity in male Sprague Dawley rat. Quantitative analysis of VAM for total phenolic (TPC), total flavonoid (TFC) and total alkaloid content (TAC) along with HPLC analysis for polyphenolics was carried out. BPA-induced testicular toxicity was determined through analysis of antioxidant enzymes, DNA damages and testicular histopathology along with reproductive hormones in serum of rat. VAM was constituted of TFC (382.50 ± 1.67 µg GAE/mg), TPC (291.17 ± 0.82 µg RE/mg), TAC (16.5 ± 0.5%), ferulic acid (2.2433 µg/mg) and vanillic acid (2.1249 µg/mg). VAM co-administration to BPA-treated rats attenuated the toxic effects of BPA and restored the body and testis weights. Altered level of luteinizing hormone (LH), testosterone and follicle-stimulating hormone (FSH) in serum, and level of antioxidants (GSH, POD, CAT and SOD) and nitric oxide in testis tissues of BPA-induced toxicity were significantly restored by VAM. Histological and comet assay studies also sanctioned the protective potential of VAM in BPA-intoxicated rats. The presence of polyphenols and alkaloids might contribute towards the scavenging and ameliorative potential of VAM in testicular toxicity induced by BPA.

An Overview of the Potential Antineoplastic Effects of Casticin.

Cancer persists as one of the leading causes of deaths worldwide, contributing to approximately 9.6 million deaths per annum in recent years. Despite the numerous advancements in cancer treatment, there is still abundant scope to mitigate recurrence, adverse side effects and toxicities caused by existing pharmaceutical drugs. To achieve this, many phytochemicals from plants and natural products have been tested against cancer cell lines in vivo and in vitro. Likewise, casticin, a flavonoid extracted from the Vitex species, has been isolated from the leaves and seeds of V. trifolia and V. agnus-castus. Casticin possesses a wide range of therapeutic properties, including analgesic, anti-inflammatory, antiangiogenic, antiasthmatic and antineoplastic activities. Several studies have been conducted on the anticancer effects of casticin against cancers, including breast, bladder, oral, lung, leukemia and hepatocellular carcinomas. The compound inhibits invasion, migration and proliferation and induces apoptosis (casticin-induced, ROS-mediated and mitochondrial-dependent) and cell cycle arrest (G0/G1, G2/M, etc.) through different signaling pathways, namely the PI3K/Akt, NF-κB, STAT3 and FOXO3a/FoxM1 pathways. This review summarizes the chemo-preventive ability of casticin as an antineoplastic agent against several malignancies.

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.

Antidiabetic and antioxidant potential of Alnus nitida leaves in alloxan induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves of Alnus nitida are used by local communities for the management of diabetes and in inflammatory disorders. METHODS: Powder of shade dried leaves of A. nitida was extracted with methanol (ANME) and fractionated in escalating polarity i.e n-hexane (ANHE), chloroform (ANCE), ethyl acetate (ANEE) and soluble residual aqueous fraction (ANAE). The extract/fractions were evaluated for antidiabetic in vitro assays; α-amylase, α-glucosidase and dipeptidyl peptidase-4 (DPP-4). The in vivo investigations were carried out on ANEE and ANAE (100 mg/kg; 200 mg/kg, p.o.) in alloxan (125 mg/kg i.p.) induced hyperglycemic rats. Serum analysis was performed on liver, pancreas and kidney function markers. Analysis of antioxidant enzymes and genotoxic studies were carried out on pancreas, liver and kidneys tissues. GC-MS analysis was performed on ANME whereas HPLC analysis was carried out on ANME, ANEE and ANAE. RESULTS: Preliminary in vitro assays indicated appreciable antidiabetic activity of ANEE and ANAE against α-amylase, α-glucosidase and DPP-4 assay. Furthermore, in vivo antidiabetic effect of ANEE and ANAE was inveterate by anti-hyperglycemic action in normal glucose loaded and diabetic glucose loaded animals. Single dose of alloxan (125 mg/kg) decreased the level of insulin and high density lipoprotein while raised the level of amylase and lipase, ALT, AST, total lipids, triglycerides, cholesterol, creatinine, BUN, CPK, CK-Mb in serum. Concentration of H2O2, lipid peroxidation (TBARS) and nitrite was increased (P < 0.05) whereas level of tissue protein, glutathione content (GSH) and antioxidant enzymes decreased in pancreas, liver and kidneys as compared to control group. Administration of ANEE and ANAE for 14 days after induction of diabetes decreased the hyperglycemia and restored the level of these parameters. Histopathological and genotoxic studies also endorsed the defensive strategies of ANEE and ANAE. GC-MS analysis of ANME demonstrated the presence of antidiabetic constituents i.e. linalool, Vitamin E and phytol. CONCLUSION: Results obtained in this study suggests antidiabetic and antioxidant abilities and provides the scientific proof of the folklore medicine.

Vincetoxicum arnottianum ameliorate inflammation by suppressing oxidative stress and pro-inflammatory mediators in rat.

ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts of Vincetoxicum arnottianum (Wight) Wight (Family Apocynaceae) are used by local communities for inflammation, healing of wound and injuries and also for urticaria. AIM OF STUDY: Extract/fractions of V. arnottianum were evaluated for potential anti-inflammatory activity in rat. METHODS: Methanol extract of aerial parts of V. arnottianum (VAM) was partitioned on polarity for n-hexane (VAH), ethyl acetate (VAE), butanol (VAB) and aqueous (VAA) fractions. The extract/fractions were evaluated during in vitro assay for protection against heat induced protein denaturation and Carrageenan induced paw inflammation in rat. VAM and VAE were evaluated for anti-inflammatory potential against formalin and Freund's complete adjuvant (FCA) induced inflammation in paw of rat while croton oil induced inflammation in ear of rat, respectively. The level of inflammatory mediators; IL-17, IL-1ß, IL-6, TNF-α and nitric oxide (NO) was estimated in serum of rat. RESULTS: All the extract/fractions used in this study exhibited anti-inflammatory activity. However, VAE (300 mg/kg) exhibited potential anti-inflammatory activity in carrageenan (78.06 ± 4.6%), formalin (54.71 ± 0.34%) and croton oil (73.12 ± 1.9%) induced edema in rat. In FCA induced inflammation model VAM and VAE showed admiring proficiencies against alteration of body weight and organ weight indices, paw edema and histological studies. In serum increased level of pro-inflammatory cytokines (IL-1ß, TNF-α, IL-6, IL-17) and NO during adjuvant-induced inflammation were more efficiently restored with VAE treatment to rat. Presence of polyphenolics; rutin, gallic acid, caffeic acid, apigenin, myricetin and quercetin was indicated in VAE. CONCLUSION: The results suggest the presence of anti-inflammatory constituents in V. arnottianum.

Evaluation of biological activities and in vivo amelioration of CCl4 induced toxicity in lung and kidney with Abutilon pannosum (G.Forst.) Schltdl. in rat.

ETHNOPHARMACOLOGICAL RELEVANCE: Abutilon pannosum is used in Pakistan for bladder inflammation, diuretic, lung disorders, diabetes and in lowering pyrexia. METHODS: Amount of total phenolic content, total flavonoid content and HPLC analysis of APM for the presence of polyphenolics were carried out. Antioxidant activity was determined by using different in vitro antioxidant assays. Amelioration effects of APM (200 mg/kg body weight and 400 mg/kg body weight) against CCl4 induced kidney and lung toxicity in rat was assessed by determining level of antioxidant enzymes, lipid peroxidation products, cytokines (TNF-α, IL-1ß and IL-2), comet assay and histological analysis. RESULTS: HPLC-DAD studies of APM indicated the presence of rutin (0.635 ± 0.011 µg/mg dry extract), gallic acid (1.07 ± 0.043 µg/mg dry extract) and catechin (0.246 ± 0.08 µg/mg dry extract) and considerable quantity of total phenolic (55.485 ± 0.85 mg GAE/g dry extract) and total flavonoid content (19.90 ± 0.58 mg Rutin/g dry extract). During in vitro antioxidant assays APM showed significant (p < 0.05) activity for iron chelation, reducing potential, inhibition of ß-carotene oxidation while moderate potential for scavenging of DPPH, hydroxyl, nitrite and phosphomolybdenum radical. Administration of CCl4 to rat severely depleted the activity level of catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD), and reduced glutathione (GSH) concentration while appreciably increased the concentration of thiobarbituric acid reactive substances (TBARS), H2O2, nitrite, TNF-α, IL-1ß and IL-2 in lung and kidney tissues of rat. Comet length, % DNA in tail and tail moment significantly (p < 0.01) increased in lung and kidney cells of CCl4 intoxicated rat. Further, injuries in lung and kidney tissues were recorded with CCl4 induced toxicity in rat. The rats treated with APM along with CCl4 exhibited an appreciable level of restoration of the altered parameters towards the control animals. CONCLUSION: The results of this study suggested the protective potential of APM in CCl4 intoxicated rats for kidney and lung injuries.

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.

Abutilon pannosum stem bark enhances the aphrodisiac activities and spermatogenesis in rat.

Abutilon pannosum (Forst.f.) Schlecht. is used for male sexual performance. In this study, we have investigated aphrodisiac potential of A. pannosum stem bark methanol extract (APM) in rat. Male rats were administered with APM (400 mg/kg) on daily basis for 5, 10 and 15 days. Time interval for mount latency, intromission latency and post-ejaculatory interval was decreased (p < .05) while time of ejaculatory latency, mount frequency, intromission frequency and ejaculatory frequency after 15 days were (p < .05) enhanced as compared to control rats. APM also increased (p < .05) penile erection index, copulatory rate and mount bout against control rats. Total count of spermatozoa was nonsignificantly increased whereas per cent of live spermatozoa and motile spermatozoa were increased (p < .05) in APM treated group after 10 and 15 days. Weight of testes, seminal vesicle, prostate and epididymis, and level of testosterone in serum increased (p < .05) after 10 and 15 days of APM administration to rat. Qualitative characterisation of APM indicated existence of alkaloids, terpenoids, coumarins, cardiac glycosides, phenols, flavonoids, saponins, tannins and sterols. Results of this study indicated aphrodisiac potential of A. pannosum in rat and may be used to enhance sexual performance in human.