Combination therapy with Hordeum vulgare, Elettaria cardamomum, and Cicer arietinum exhibited anti-diabetic potential through modulation of oxidative stress and proinflammatory cytokines.

Poly-herbal therapies for chronic diseases like diabetes mellitus (DM) have been practiced in south Asia for centuries. One of such therapies comprises of Hordeum vulgare, Elettaria cardamomum and Cicer arietinum that have shown encouraging therapeutic potential in the treatment of diabetes and obesity. Therefore, poly-herbal granules (PHGs) of this formula were developed and investigated for their anti-diabetic and anti-obesity potential in obese-diabetic rats. The developed PHGs were chemical characterized and the virtual molecular docking was performed by Discovery studio visualizer (DSV) software. For in-vivo experiment, obesity in rats was induced with high-fat high-sugar diet. After that, diabetes was induced by alloxan monohydrate 150 mg/kg i.p. injection. The diseased rats were treated with PHGs at 250, 500 and 750 mg/kg/day for four weeks. GC-MS analysis of PHGs demonstrated the presence of 1,3-Benzenedicarboxylic acid bis(2-ethylhexyl) ester and 1,2-Benzenedicarboxylic acid di-isooctyl ester and phenol, 2,4-bis(1,1-dimethylethyl). Molecular docking of these compounds demonstrated higher binding energies with receptor than metformin against α-amylase and α-glucosidase. PHGs exhibited a decline in body weight, HbA1c, hyperlipidemia, hyperglycemia, and insulin resistance in diseased rats. The histopathological examination revealed that PHGs improved the alloxan-induced damage to the pancreas. Furthermore, PHGs increased the SOD, CAT and GSH while and the decreased the level of MDA in the liver, kidney and pancreas of diseased rats. Additionally, the PHGs had significantly downregulated the TNF-α and NF-κB while upregulated the expression of NrF-2. The current study demonstrated that the PHGs exhibited anti-diabetic and anti-obesity potential through amelioration of oxidative stress, NF-κB, TNF-α, and NrF-2 due to the presence of different phytochemicals.

A comprehensive review on the applications of ferrite nanoparticles in the diagnosis and treatment of breast cancer.

Various conventional treatments including endocrine therapy, radiotherapy, surgery, and chemotherapy have been used for several decades to treat breast cancer; however, these therapies exhibit various life-threatening and debilitating adverse effects in patients. Additionally, combination therapies are required for prompt action as well as to prevent drug resistance toward standard breast cancer medications. Ferrite nanoparticles (NPs) are increasingly gaining momentum for their application in the diagnosis and treatment of breast cancer. Spinel ferrites are particularly used against breast cancer and have shown in vitro and in vivo better efficacy as compared to conventional cancer therapies. Magnetic resonance imaging contrast agents, magnetic particle imaging tracers, cell separation, and immune assays are some aspects related to the diagnosis of breast cancer against which different ferrite NPs have been successfully evaluated. Moreover, citrate-coated nickel ferrite, Mg/Zn ferrites, poly amidoamine dendrimers, cobalt ferrites, graphene oxide cobalt ferrites, doxorubicin functionalized cobalt ferrites, chitosan-coated zinc ferrites, PEG-coated cobalt ferrite, and copper ferrite NPs have demonstrated antiproliferative action against different breast cancer cells. Oxaliplatin-loaded polydopamine/BSA-copper ferrites, functionalized cobalt and zinc ferrites of curcumin, oxaliplatin-copper ferrite NPs, tamoxifen/diosgenin encapsulated ZnO/Mn ferrites, and fabricated core-shell fibers of doxorubicin have been developed to increase the bioavailability and anti-proliferative effect and decrease the toxicity of anticancer drugs. These ferrite NPs showed an anticancer effect at different doses in the presence or absence of an external magnetic field. The present review covers the in-depth investigations of ferrite NPs for the diagnosis and management of breast cancer.

Appraisal of anti-arthritic potential of Coronopus didymus (L.) Sm. aqueous extract and its safety study in Wistar rats.

The current study aimed to find out the anti-arthritic activity and safety study of Coronopus didymus aqueous extract (CDAE) as well as its chemical characterization by HPLC-DAD. Safety study including acute and subacute toxicity studies of the plant aqueous extract was also performed. In complete Freund's adjuvant-induced arthritic model (CFA), 0.15 ml CFA was injected in the left hind paw at day 1 in all rats except normal rats. Treatment with CDAE at 200, 400, and 800 mg/kg and methotrexate (1 mg/kg) was administered at day 8 and continued till 28th day using oral gavage. The CDAE considerably (p < 0.05) reduced the paw swelling and arthritic score, and reinstated the body weight and blood parameters. The CDAE considerably modulated superoxide dismutase, catalase, reduced glutathione, and malondialdehyde level in liver homogenate in contrast to disease control. The CDAE at 400 mg/kg considerably reduced IL-6, IL -1ß, COX-2, and NF-ĸß, whereas elevated IL-10, IL-4, and I-kappa ß as equated to disease and standard groups. The LD50 of CDAE > 2000 mg/kg. In subacute toxicity study, CDAE at 200-800 mg/kg did not exhibit clinical signs of toxicity, mortality, hematological, biochemical, and histological alteration in the liver heart, kidney, and lungs in contrast to the normal group. It was concluded that the presence of delphinidine-3-glucoside, diosmetin, 3-feruloyl-4,5-dicaffeoyl quinic acid, and gallic acid in CDAE might be accountable for its anti-arthritic activity and safe use for a long period.

Chemical characterization, antioxidant and antidiabetic activities of a novel polyherbal formulation comprising of Hordeum vulgare, Elettaria cardamomum and Cicer arietinum extracts.

Diabetes mellitus (DM) is the most prevalent endocrine disorder. Numerous individual herbs possess anti-diabetic activity. The seeds of Hordeum vulgare, Elettaria cardamomum and Cicer arietinum are traditionally used to manage DM. The ambition of this work was to formulate the poly-herbal granules (PHGs) comprising of these three functional foods and evaluate their in-vitro antioxidant and antidiabetic potential. The dried seed extracts of Hordeum vulgare, Elettaria cardamomum and Cicer arietinum were used in a ratio of 2.5:1:1 to formulate PHGs by wet granulation method. The ratio of extracts was selected on the basis of traditional phytotherapies popularly used by local Hakeems of Pakistan to achieve glycemic control in diabetic patients resistant to traditional allopathic regime of medicine. The flow properties of developed PHGs were evaluated. The UV-Visible spectroscopic, Fourier Transform Infrared (FTIR) and HPLC-DAD of all seed extracts and PHGs were performed. The in-vitro antioxidant DPPH, FRAP, total antioxidant capacity (TAC) and Nitric Oxide (NO) scavenging assays were carried out on PHGs. The in-vitro antidiabetic activity of PHGs was investigated by alpha-amylase and alpha-glucosidase enzyme inhibition activity. The developed PHGs exhibited excellent flow properties. The UV-Vis spectra of all seed extracts and PHGs demonstrated peak at 278 nm showing the presence of flavonoids and phenols. The FTIR spectra confirmed the existence of flavonoids, and phenols along with amines in seed extracts as well as PHGs. The HPLC-DAD test revealed the existence of gallic acid, ascorbic acid, Quercetin-3-(caffeoyldiglucoside)-7-glucoside, Rosmarinic acid, delphinidin-3,5-diglucosides, Kaempferol-3-feruloylsophoroside-7-glucoside and Phloroglucinol in PHGs. The PHGs exhibited IC50 of 51.23, 58.57, 55.41 and 53.13 µg/mL in DPPH assay, FRAP assay, TAC, Nitric oxide scavenging assays respectively. The PHGs also demonstrated IC50 of 49.97 and 36.16 µg/mL in alpha-amylase and in alpha-glucosidase inhibition assays respectively in dose dependent manner. The developed PHGs exhibited an excellent flow property. These exhibit significant in-vitro antioxidant and antidiabetic profile by virtue of flavonoid and phenolic acid derivatives.

Nanotechnology-Based Drug Delivery Approaches of Mangiferin: Promises, Reality and Challenges in Cancer Chemotherapy.

Mangiferin (MGF), a xanthone derived from Mangifera indica L., initially employed as a nutraceutical, is now being explored extensively for its anticancer potential. Scientists across the globe have explored this bioactive for managing a variety of cancers using validated in vitro and in vivo models. The in vitro anticancer potential of this biomolecule on well-established breast cancer cell lines such as MDA-MB-23, BEAS-2B cells and MCF-7 is closer to many approved synthetic anticancer agents. However, the solubility and bioavailability of this xanthone are the main challenges, and its oral bioavailability is reported to be less than 2%, and its aqueous solubility is also 0.111 mg/mL. Nano-drug delivery systems have attempted to deliver the drugs at the desired site at a desired rate in desired amounts. Many researchers have explored various nanotechnology-based approaches to provide effective and safe delivery of mangiferin for cancer therapy. Nanoparticles were used as carriers to encapsulate mangiferin, protecting it from degradation and facilitating its delivery to cancer cells. They have attempted to enhance the bioavailability, safety and efficacy of this very bioactive using drug delivery approaches. The present review focuses on the origin and structure elucidation of mangiferin and its derivatives and the benefits of this bioactive. The review also offers insight into the delivery-related challenges of mangiferin and its applications in nanosized forms against cancer. The use of a relatively new deep-learning approach to solve the pharmacokinetic issues of this bioactive has also been discussed. The review also critically analyzes the future hope for mangiferin as a therapeutic agent for cancer management.

Curative potential of Populus ciliata Wall ex. Royle extract against adjuvant-induced arthritis and peripheral neuropathy in Wistar rats.

Populus ciliata (PCCR) is traditionally used to treat muscular swelling, inflammation, pain, and fever. The current study was designed to validate the potential of aqueous ethanolic extract of the plant against inflammation, peripheral neuropathy, and pain in arthritic rats. The PCCR was chemically characterized by gas chromatography-mass spectroscopy and high-performance liquid chromatography. In vitro antioxidant, and in vitro anti-inflammatory assays were carried out on PCCR. For anti-arthritic potential, Wistar rats' rear paws were injected with 0.1 ml Complete Freund's Adjuvant using methotrexate (3 mg/kg/week) as standard control. PCCR at 100, 200, and 400 mg/kg was given orally to arthritic rats for 21 days. The PCCR exhibited significant inhibition of bovine serum albumin denaturation (IC-50: 202.1 µg/ml), egg albumin denaturation (IC-50:553.5 mg/ml) and RBC membrane stabilization (IC-50: 122.5 µg/ml) and antioxidant (IC-50 = 49.43 µg/ml) activities. The PCCR notably decreased the paw diameter and increased body weight of treated arthritic animals as equated to diseased control. The treatment notably (p < 0.05-0.0001) decreased malondialdehyde, and increased superoxide dismutase, reduced glutathione, and catalase in the liver and sciatic nerve homogenate in compared to diseased rats. The PCCR treatment remarkably (p < 0.05-0.0001) regulated the levels of nor-adrenaline and serotonin in sciatic nerve in contrast to diseased rats. Treatment with PCCR improved the motor activity, pain, ligament degeneration, and synovial hyperplasia in arthritic rats. Moreover, PCCR significantly (p < 0.01-0.0001) decreased the IL-6 and TNF-α. It is evident from the current study that PCCR had ameliorated polyarthritis and peripheral neuropathy through reduction of inflammatory markers, and improvement of oxidative stress might be due to presence of phenolic acids, flavonoids, phytosterols, and other fatty acids.

Toxicity profiling of Burgmansia aurea Lagerh. Leaves using acute and sub-acute toxicity studies in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Toxicity studies in appropriate animal models are an integral and very important component of pre-clinical studies in drug development. Brugmansia aurea lagerh. is used for both medicinal and non-medical purposes, including treating skin infections, different types of physical discomfort, inflammation, cough, hallucinations, and evil protection. AIM OF THE STUDY: This study was designed to detect any hazardous effects of B. aurea on animals and find out its LD50. MATERIALS & METHODS: An acute toxicity study was performed to find out the LD50 value and sub-acute toxicity study was performed to find out the toxicity on repeated dose administration till 28 days. Both studies were performed according to the organization of economic cooperation and development (OECD) 425 and 407 respectively. For the acute oral toxicity study, animals were divided into two groups, group I normal control (NC) and group II received a 2000mg/kg dose of B.aurea leaves extract. In the sub-acute toxicity study, male and female animals were divided into eight groups, I-IV for males and V-VIII for females received control, 100, 200 & 400mg/kg B. aurea leaves extract respectively. Hematological and biochemical markers were estimated at the end of each study. RESULTS: Results revealed that no mortality and morbidity were observed in acute oral as well as sub-acute toxicity studies. Oxidative stress markers were increased significantly in all organs of the treatment groups in both studies. Animals significantly decreased their food and water intake in an acute oral toxicity study. A slight difference in renal function tests was observed in the acute oral toxicity study when compared with the normal control group. No significant change in histopathology was observed in both studies on selected organs. CONCLUSION: This study concluded that B. aurea can be safely used for pharmacological purposes.

"Ficus johannis Boiss. leaves ethanolic extract ameliorate streptozotocin-induced diabetes in rats by upregulating the expressions of GCK, GLUT4, and IGF and downregulating G6P".

The leaves of Ficus johannis Boiss (F. johannis), commonly known as Fig tree, Anjir, and Teen, are used by the folk medicinal practitioners in Iran for controlling hyperglycemia in diabetic patients. This study investigated the pharmacological basis for antidiabetic effect of the ethanolic extract of F. johannis leaves using in vitro and in vivo experimental models. Qualitative screening of phytochemicals, estimation of total phenolic and flavonoid contents, and in vitro antioxidant and α-amylase inhibition assays were performed. Moreover, the High-performance liquid chromatography (HPLC) quantification, acute toxicity, glucose tolerance, and in vivo antidiabetic effect along with the evaluation of gene expressions involved in diabetes mellitus were carried out. Significant quantities of phenolic (71.208 ± 2.89 mgg-1 GAE) and flavonoid (26.38 ± 3.53 mgg-1 QE) were present. Inhibitory concentration (IC50) of the plant extract exhibited an excellent in vitro antioxidant (IC50 = 33.81 µg/mL) and α-amylase (IC50 = 12.18 µg/mL) inhibitory potential. The HPLC analysis confirmed the gallic acid (257.79 mgg-1) as main constituent of the extract followed by kaempferol (22.86 mgg-1), myricetin (0.16 mgg-1), and quercetin (3.22 mgg-1). Ethanolic extract displayed glucose tolerance in normo-glycemic rats. Streptozotocin-induced hyperglycemia declined dose dependently in the extract treated rats with improvement in lipid profile and liver and renal function biomarkers. The F. johannis-treated groups showed an increase in mRNA expressions of glucose transporter 4 (GLUT-4), glucokinase, insulin growth like factor 1 and peroxisomal proliferator activating receptor gamma in pancreas. However, the Glucose-6-phosphatase was downregulated. Present study suggests that the ethanolic extract of F. johannis leaves demonstrates a good anti-diabetic profile by improving insulin sensitivity, GLUT-4 translocation, and carbohydrate metabolism while inhibiting lipogenesis.

Mechanistic insights on the possible protective role of polyphenols extracted from Tamarix aphylla aerial parts against sodium arsenite-induced hepatotoxicity in rats.

Arsenic exposure is associated with the induction of hepatotoxicity. Current study was aimed to investigate the hepato-protective ability of polyphenolic components of Tamarix aphylla (TA) ethanolic extract against sodium arsenite (SA)-induced liver injury of rats. Significantly higher quantities of phenolic (318.7±2.5 mgg-1GAE) and flavonoid (250.69 ±3.3 mgg-1QE) contents were present. Inhibitory concentration (IC50) exhibited an excellent potential for antioxidant (IC50= 25.99 µg/mL) assay. High performance liquid chromatography (HPLC) confirmed the existence of myercetin (10.40ppm), sinapic acid (2.131ppm), kaempferol (0.486ppm), caffeic acid (5.094 ppm). Forty-two rats were divided into 7 groups. Group 1 received normal saline (2 mL/kg/day, orally for 21 days), Group 2 received SA (10mg/kg/day for 21 days), and Group 3 received SA alone for 7 days (10mg/kg) and continues with silymarine for 21 days (25mg/kg orally). Group 4, 5, 6 received SA alone for 7 days and continue with TA extract up to 21 days (125mg/kg, 250mg/kg, and 500mg/kg orally) respectively, and Group 7 received TA extract (500mg/kg) for 21 days. SA was administered to all treated groups for 21 days. Treatment with polyphenolic ethanolic extract of TA restored the hepatic indices and oxidative markers in a dose-dependent manner. The upregulation in tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2 upon SA treatment suggesting inflammation was normalized by the treatment of rats. Above mentioned biochemical findings were supported well with histopathological screening. Present findings suggest that TA polyphenolic ethanolic extract could mitigate the oxidative stress and inflammation induced by SA in liver tissue.

Development and In Vitro/Ex Vivo Evaluation of Lecithin-Based Deformable Transfersomes and Transfersome-Based Gels for Combined Dermal Delivery of Meloxicam and Dexamethasone.

Transfersomes (TFS) are the promising carriers for transdermal delivery of various low and high molecular weight drugs, owing to their self-regulating and self-optimizing nature. Herein, we report synthesis and characterization of TFS loaded with meloxicam (MLX), an NSAID, and dexamethasone (DEX), a steroid, for simultaneous transdermal delivery. The different formulations of TFS containing varying amounts of lecithin, Span 80, and Tween 80 (TFS-1 to TFS-6) were successfully prepared by thin-film hydration method. The size of ranged between 248 and 273 nm, zeta potential values covering from -62.6 to -69.5 mV, polydispersity index (PDI) values in between 0.329 and 0.526, and entrapment efficiency of MLX and DEX ranged between 63-96% and 48-81%, respectively. Release experiments at pH 7.4 demonstrated higher cumulative drug release attained with Tween 80 compared to Span 80-based TFS. The scanning electron microscopy (SEM) of selected formulations -1 and TFS-3 revealed spherical shape of vesicles. Furthermore, three optimized transfersomal formulations (based on entrapment efficiency, TFS-1, TFS-3, and TFS-5) were incorporated into carbopol-940 gels coded as TF-G1, TF-G3, and TF-G5. These transfersomal gels were subjected to pH, spreadability, viscosity, homogeneity, skin irritation, in vitro drug release, and ex vivo skin permeation studies, and the results were compared with plain (nontransfersomal) gel having MLX and DEX. TFS released 71.72% to 81.87% MLX in 12 h; whereas, DEX release was quantified as 74.72% to 83.72% in same time. Nevertheless, TF-based gels showed slower drug release; 51.54% to 59.60% for MLX and 48.98% to 61.23% for DEX. The TF-G systems showed 85.87% permeation of MLX (TF-G1), 68.15% (TF-G3), and 68.94% (TF-G5); whereas, 78.59%, 70.54%, and 75.97% of DEX was permeated by TF-G1, TF-G3, and TF-G5, respectively. Kinetic modeling of release and permeation data indicated to follow Korsmeyer-Peppas model showing diffusion diffusion-based drug moment. Conversely, plain gel influx was found mere 26.18% and 22.94% for MLX and DEX, respectively. These results suggest that TF-G loaded with MLX and DEX can be proposed as an alternate drug carriers for improved transdermal flux that will certainly increase therapeutic outcomes.

Wound Healing Potential and In Silico Appraisal of Convolvulus arvensis L. Methanolic Extract.

Convolvulus arvensis L. is rich in phenolic compounds and traditionally used to treat wounds, skin ulcer, and inflammation. The current study is aimed at scientifically potentiating its traditional wound healing use. The methanolic extract of C. arvensis stem (CaME) was analyzed for HPLC and GC-MS analyses. The binding modes of active compounds were investigated against protein targets glycogen synthase kinase-3ß (GSK-3ß), transforming growth factor-beta (TGF-ß), c-myc, and ß-catenin by molecular docking followed by molecular dynamic simulations which revealed some conserved mode of binding as reported in crystal structures. The antioxidant potential of CaME was evaluated by in vitro methods such as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, hydrogen peroxide scavenging, and ferric reducing power assays. Ointment formulations of 10 and 20% CaME were applied topically and evaluated for wound healing potency against the excisional wound on the skin of Wistar rats. Gentamycin (0.1%) served as standard therapy. The healing process was observed for 20 days in the form of wound size and epithelialization followed by histopathological evaluation of the wound area. Chemical characterization showed the presence of 7-hexadecenoic acid, 2-hexadecylicosan-1-ol, quercetin, gallic acid, ferulic acid, and other compounds. The plant extract exhibited significant in vitro antioxidant activity. The animals treated with 10% ointment showed moderate healing, whereas the treatment with 20% CaME revealed healing potential comparable to the standard 0.1% gentamycin as coevidenced from histopathological evaluation of skin. The study corroborates promising potential of C. arvensis on the healing of wounds, which possibly will be attributed to its antioxidant activity, fatty acids, quercetin, and gallic and caffeic acids, and binding potential of its phytoconstituents (phenolic acids) with wound healing targets.

In Vitro and In Vivo Anti-Arthritic Potential of Caralluma tuberculata N. E. Brown. and Its Chemical Characterization.

Present research was planned to assess the in vitro and in vivo anti-arthritic potential of Caralluma tuberculata N. E. Brown. methanolic (CTME) and aqueous (CTAQ) extracts. Chemical characterization was done by high-performance liquid chromatography and gas chromatography−mass spectrometry analysis. The Complete Freund's Adjuvant (CFA) was injected in left hind paw of rat at day 1 and dosing at 150, 300 and 600 mg/kg was started on the 8th day via oral gavage in all groups except normal and disease control rats (which were given distilled water), whereas methotrexate (intraperitoneal; 1 mg/kg/mL) was administered to standard control. The CTME and CTAQ exerted significant (p < 0.01−0.0001) in vitro anti-arthritic action. Both extracts notably reduced paw edema, and restored weight loss, immune organs weight, arthritic score, RBCs, ESR, platelet count, rheumatoid factor (RF), C-reactive protein, and WBCs in treated rats. The plant extracts showed significant (p < 0.05−0.0001) downregulation of tumor necrosis factor-α, Interleukin-6, -1ß, NF-κB, and cyclooxygenase-2, while notably upregulated IL-4, IL-10, I-κBα in contrast to disease control rats. The plant extracts noticeably (p < 0.001−0.0001) restored the superoxide dismutase and catalase activities and MDA levels in treated rats. Both extracts exhibited significant anti-arthritic potential. The promising potential was exhibited by both extracts probably due to phenolic, and flavonoids compounds.

Antidiabetic Potential and Antioxidant Activity of Olea europaea subsp. Cuspidata (Indian Olive) Seed Extracts.

The aim of the present study was to evaluate the antioxidant and antidiabetic potential of Indian olive seed extracts. Plant seeds were sequentially extracted with n-hexane, chloroform, methanol, and water. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging and alpha-amylase inhibitory activities of extracts were carried out. Olea europaea methanolic extract (MEOE) and aqueous extract (AEOE) were orally administered to normoglycemic and alloxan-treated diabetic rats so as to determine their hypoglycemic effect. High-performance liquid chromatography (HPLC) analysis showed gallic acid, ferulic acid, quercetin, and vanillic acid in MEOE. It was found that the methanolic and aqueous extracts exhibited the maximum DPPH and alpha-amylase inhibition activities, respectively. MEOE and AEOE exerted a significant decline in the fasting blood sugar in diabetic animals (p < 0.05); however, they did not cause hypoglycemia in nondiabetic animals. Treatment with MEOE and AEOE reduced the aggravated liver and kidney function biomarkers. Aggravated levels of oxidative stress biomarkers including superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and malondialdehyde (MDA) were restored by treatment with MEOE. Moreover, MEOE improved the count of islets of Langerhans in the pancreas, fatty changes, and enlarged sinusoidal spaces in the liver and necrosis of the glomerulus and tubular cells of the kidney in diabetic rats. This study showed that the African olive seed extract effectively managed experimental diabetes and restored the normal functions and histology of the liver and kidney in diabetic rats through the reduction of oxidative stress.

Hepatoprotective effect of Cordia rothii extract against CCl4-induced oxidative stress via Nrf2-NFκB pathways.

Cordia rothii Roem. & Schult. possesses various beneficial effects and is traditionally used in folk medicine against liver diseases but its molecular mechanism remains unclear. Antioxidant and hepatoprotective effects of Cordia rothii methanolic fraction (CRMF) were investigated in CCl4-induced liver injury. Antioxidant effects were evaluated using DPPH assay, ferric thiocyanate (FTC) assay, and HepG2 cells. A qualitative analysis of phytochemicals was carried out by gas chromatography-mass spectrometry (GC-MS). The hepatoprotective effects of CRMF were assessed against CCl4-induced liver damage in rats. Our results showed that CRMF significantly increased cell viability against CCl4-induced HepG2 cells. The in vivo results showed that CRMF significantly reduced the level of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, hepatic antioxidant enzymes, including superoxide dismutase, malondialdehyde, and increased glutathione level. Normal hepatocyte integrity and microstructures were observed in histopathological results. Furthermore, the mRNA level of inflammatory mediators including interleukon (IL)-1ß, IL-6, TNF-α, nuclear factor kappa B (NF-KB), IL-10 and nuclear factor-erythroid factor 2-related factor 2 (NrF2) were reverted in CRMF pretreatment groups. Thus, CRMF exhibited strong antioxidant, and hepatoprotective activities, which may involve Nrf2-NFκB pathways.

Pterostilbene improves CFA-induced arthritis and peripheral neuropathy through modulation of oxidative stress, inflammatory cytokines and neurotransmitters in Wistar rats.

Pterostilbene is a stilbene flavonoid that occurs naturally in various plants as well as produced by genetic engineering. It exhibits anti-inflammatory, analgesic, anti-oxidant and neuroprotective activities. This research was aimed to determine the potential of pterostilbene against arthritis and peripheral neuropathy in Complete Freund's Adjuvant (CFA) induced arthritis. Rat hind paw was injected with 0.1 ml CFA to induce arthritis. Standard control animals received oral methotrexate (3 mg/kg/week). Pterostilbene at 12.5, 25 and 50 mg/kg was given orally to different groups of arthritic rats from day 7-28 for 21 days. Pterostilbene significantly reduced paw diameter and retarded the decrease in body weight of arthritic rats. It profoundly (p < 0.05-0.0001) reduced lipid peroxidation and nitrites, while increased superoxide dismutase (SOD) in the liver tissue. Pterostilbene treatment significantly (p < 0.0001) reduced TNF-α and IL-6 levels. Pterostilbene markedly improved (p < 0.05-0.001) motor activity and showed analgesic effect in arthritic rats at 25 and 50 mg/kg as compared to disease control rats. Furthermore, it notably (p < 0.05-0.0001) increased SOD activity, nitrites, noradrenaline and serotonin levels in the sciatic nerve of arthritic rats. Treatment with pterostilbene also ameliorated the CFA-induced pannus formation, cartilage damage and synovial hyperplasia in the arthritic rat paws. It is determined from the current study that pterostilbene was effective in reducing CFA-induced arthritis in rats through amelioration of oxidative stress and inflammatory mediators. It was also effective to treat peripheral neuropathy through modulation of oxidative stress and neurotransmitters in sciatic nerves.

HPLC-DAD analysis of Quercus leucotrichophora extract and appraisal of its antiasthmatic potential via modulation of aquaporins, inflammatory, and oxidative stress biomarkers in Albino mice.

Herbal drugs offer an alternative approach for the treatment of diseases like asthma due to low cost and comparatively less adverse effects in contrast to synthetic drugs. Leaves of Quercus leucotrichophora are traditionally used for the treatment of asthma. The study was aimed to assess the anti-asthmatic activity of Quercus leucotrichophora (QL) methanolic (QLME) and aqueous extracts (QLAE) in ovalbumin-(OVA) induced asthma and chemical characterization of QL extract by High Performance Liquid Chromatography-Diode array detector (HPLC-DAD). Animals were inoculated with OVA (i.p) on day 1 and 14 followed by intranasal challenge on 27th and 29th day. Both extracts of QL at 600, 300 and 150 mg/kg and dexamethasone (2 mg/kg) l were administered consecutively from days 15-26 via oral gavage. The QL extracts notably reduced (p < 0.0001-p < 0.05) total and differential leukocyte counts in blood and BALF and serum IgE levels in contrast to disease control. Both extracts and Dex substantially improved activities of superoxide dismutase, catalase, and GSH, while reduced malondialdehyde level in treated mice. Treatment with extracts and Dex caused significant (p < 0.0001-p < 0.05) downregulation of tumor necrosis factor-α, interleukin-4, - 5, - 13, - 6, - 1ß, and NF-κB whereas, increased expression of Aquaporin (AQP) 1 and AQP5 in contrast to disease control. It was inferenced from findings that both extract of QL exhibited notable antiasthmatic potential might be due to presence of Daidzein-glucuronic acid, 3-Hydroxyphloretin 6'-hexoside, Catechin, Quercetin, and Kaemferol.

Comparative Potential of Zinc Sulfate, L-Carnitine, Lycopene, and Coenzyme Q10 on Cadmium-Induced Male Infertility.

The human exposure to toxic chemicals and heavy metals is one of the main predisposing factors contributing to male infertility. Acute exposure to cadmium chloride results in testicular damage and infertility. The purpose of the present study was to investigate and compare the curative effect of coenzyme Q10 (CoQ10), lycopene, L-carnitine (LC), and zinc sulfate against the cadmium-induced infertility in male Wistar rats. Cadmium chloride (0.4 mg/kg/day) was orally administered to rats for three consecutive days. Then, oral administration of different treatments (i.e., LC 100 mg/kg, CoQ10 20 mg/kg, lycopene 4 mg/kg, zinc sulfate 6 mg/kg, and a combination LC-CoQ10 at 500/50 mg/kg) was carried out for 30 days. The impact of different treatments on semen parameters, such as sperm count and motility, testicular antioxidants, and serum testosterone, was determined. Furthermore, the morphology of epididymis sperms and histopathology of rat testes were also assessed. Cadmium exposure decreased the sperm count, progressive sperm motility, testosterone, superoxide dismutase (SOD), and catalase and reduced glutathione (GSH). It also caused banana sperm tail, bent sperm head, vacuolization of seminiferous tubules, and oligospermia in rat testes. All treatments with nutraceuticals improved sperm count, sperm morphology, serum testosterone, vacuolization of seminiferous tubules, and oligospermia in diseased rats. Treatment with lycopene, LC, and LC-CoQ10 improved progressive sperm motility and other parameters and increased SOD, GSH, and CAT in the rat testes. CoQ10 also increased SOD activity in rat testes' tissue homogenates. It is concluded from the current study that all nutraceuticals partially improved reproductive toxicity of cadmium. The administration of lycopene and a high-dose combination of LC-CoQ10 were more efficacious in treating cadmium-induced infertility than other treatments. Treatment of cadmium-exposed rats with lycopene, LC, CoQ10, and LC-CoQ10 improved sperm count and motility through reduction of testicular oxidative stress and improving serum testosterone.

Therapeutic potential of Ceratonia siliqua extract for the management of asthma and hypertension.

The current work was performed to explore the pharmacological mechanisms involved in the management of asthma and hypertension along with the safety profile of the Ceratonia siliqua (C. siliqua/Carob) pods. The bronchorelaxant, vasorelaxant, and cardioselective activities of C. siliqua pods were investigated using isolated rabbit tracheal, aortic, and paired atrial fragments on the Power lab data acquisition system. Normotensive rats were used to study antihypertensive activity. The plant extract and its fractions relaxed the carbachol-induced contraction in the tracheal fragments and shifted the concentration-response curve of carbachol towards the right confirming the muscarinic receptor antagonist activity. The relaxation of phenylephrine-induced contraction in an aortic fragment by the extract showed α- adrenergic blocking activity. Furthermore, the extract produced a cardio-selective response in the paired atria and decreased the blood pressure in anesthetized normotensive rats. The plant extract proved to be non-toxic in oral acute and chronic toxicity studies and did not demonstrate any sign of histopathological lesions. These results suggested that the plant extract was non-toxic and could be used in the management of lifetime therapies of respiratory and cardiovascular disorders without any unwanted effects.

Ameliorating Effect of Malva neglecta Wallr on Obesity and Diabetes in Wistar Rats: A Mechanistic Study.

A high caloric food causes deposition of fats that may progress to obesity. Obesity is a risk factor for various metabolic and cardiovascular diseases, including but limited to diabetes mellitus. This study is aimed at determining the ameliorating effect of Malva Neglecta wallr aqueous-methanolic extract (MNME) on obesity and diabetes in Wistar rats. The MNME was chemically characterized by high-performance liquid chromatography (HPLC). The plant extract was evaluated by in vitro α-amylase inhibition and DPPH scavenging activities. Obesity was induced by administering high sugar and fat diet (HSFD) to rats for six weeks, followed by intraperitoneal injection of alloxan monohydrate (150 mg/kg) to induce diabetes. Oral treatments with MNME 250, 500, and 750 mg/kg/day were given to diabetic obese rats for 14 days. The HPLC analysis showed the presence of phenolic acids and flavonoids. The plant extract showed significant antioxidant (P < 0.001) and alpha-amylase (P < 0.0001) inhibition activities. The administration of MNME displayed a considerable decrease in fasting blood glucose, body weight, liver function tests, urea, cholesterol, leptin, and insulin levels in diabetic obese rats as compared to the disease control group and maximum effect were observed at 750 mg/kg/day of MNME. The MNME significantly increased (P < 0.05 - 0.001) the levels of GSH, SOD, and CAT in the liver, kidney, and pancreas while notably (P < 0.05 - 0.001) reduced the malondialdehyde level in kidney and pancreas of diabetic obese rats in contrast to disease control rats. This experimental study concludes that the MNME had exhibited antiobesity and antidiabetic activities through reduction of oxidative stress, leptin, α-amylase activity, and insulin resistance due to the presence of phenolic acid and flavonoid compounds.

Alternative Therapy of Psychosis: Potential Phytochemicals and Drug Targets in the Management of Schizophrenia.

Schizophrenia is a chronic mental and behavioral disorder characterized by clusters of symptoms including hallucinations, delusions, disorganized thoughts and social withdrawal. It is mainly contributed by defects in dopamine, glutamate, cholinergic and serotonergic pathways, genetic and environmental factors, prenatal infections, oxidative stress, immune system activation and inflammation. Management of schizophrenia is usually carried out with typical and atypical antipsychotics, but it yields modest benefits with a diversity of side effects. Therefore, the current study was designed to determine the phytochemicals as new drug candidates for treatment and management of schizophrenia. These phytochemicals alter and affect neurotransmission, cell signaling pathways, endocannabinoid receptors, neuro-inflammation, activation of immune system and status of oxidative stress. Phytochemicals exhibiting anti-schizophrenic activity are mostly flavonoids, polyphenols, alkaloids, terpenoids, terpenes, polypropanoids, lactones and glycosides. However, well-designed clinical trials are consequently required to investigate potential protective effect and therapeutic benefits of these phytochemicals against schizophrenia.