Effectiveness of ayurvedic formulation, NAOQ19 along with standard care in the treatment of mild-moderate COVID-19 patients: A double blind, randomized, placebo-controlled, multicentric trial.

BACKGROUND: Medicines in indigenous systems such as Ayurveda have strong antimicrobial activity but double-blind randomized control trials are infrequent in this system of medicine. The efficacy of a new ayurvedic formulation was evaluated during the pandemic. METHODS: 150 mild-moderate COVID-19 patients were enrolled and randomized in 1:1 to NAOQ19 and placebo group. RT-PCR was done on Day 3, 5 and 7. CBC, CRP, LFT, and KFT were assessed at baseline and exit. Duration of hospital stay was noted and clinical assessment was also performed. RESULT: The results demonstrated more people turning RT-PCR negative in the NAOQ19 group compared to the placebo group on day 3 (p-value = 0.033). The mean time duration to turn RT-PCR negative was significantly lower in the NAOQ19 group (4.6 days) compared to placebo group (5.2 days) (p-value = 0.018). There was significant reduction in hospital stay among patients in the NAOQ19 arm who were discharged earlier (5.6 days) compared to placebo group (6.4 days) (p-value = 0.046). Patients in NAOQ19 arm did not show any adverse life-threatening events. CONCLUSION: The ayurvedic preparation given along with standard of care therapy reduced the duration of hospital stay and there was earlier conversion to RT-PCR negative.The integrated approach can help to reduce patient workload in the hospitals as well as limit the transmission of the virus in the community. STUDY REGISTRATION: CTRI/2021/05/033790.

A citrate efflux transporter important for manganese distribution and phosphorus uptake in rice.

The plant citrate transporters, functional in mineral nutrient uptake and homeostasis, usually belong to the multidrug and toxic compound extrusion transporter family. We identified and functionally characterized a rice (Oryza sativa) citrate transporter, OsCT1, which differs from known plant citrate transporters and is structurally close to rice silicon transporters. Domain analysis depicted that OsCT1 carries a bacterial citrate-metal transporter domain, CitMHS. OsCT1 showed citrate efflux activity when expressed in Xenopus laevis oocytes and is localized to the cell plasma membrane. It is highly expressed in the shoot and reproductive tissues of rice, and its promoter activity was visible in cells surrounding the vasculature. The OsCT1 knockout (KO) lines showed a reduced citrate content in the shoots and the root exudates, whereas overexpression (OE) line showed higher citrate exudation from their roots. Further, the KO and OE lines showed variations in the manganese (Mn) distribution leading to changes in their agronomical traits. Under deficient conditions (Mn-sufficient conditions followed by 8 days of 0 µm MnCl2 · 4H2 O treatment), the supply of manganese towards the newer leaf was found to be obstructed in the KO line. There were no significant differences in phosphorus (P) distribution; however, P uptake was reduced in the KO and increased in OE lines at the vegetative stage. Further, experiments in Xenopus oocytes revealed that OsCT1 could efflux citrate with Mn. In this way, we provide insights into a mechanism of citrate-metal transport in plants and its role in mineral homeostasis, which remains conserved with their bacterial counterparts.

Ayurvedic Treatment in the Rehabilitation of Ischemic Stroke Patients in India: A Randomized Controlled Trial Study Protocol.

In patients with ischemic stroke, motor and sensory impairments are common and are associated with functional disability. Conventional physiotherapy (CP) is the primary modality of rehabilitation for post-stroke sensorimotor dysfunction. Ayurveda is a commonly practiced alternative system of medicine that offers unique rehabilitative measures for post-stroke recovery. We hypothesize that Ayurvedic rehabilitative treatment (ART) is superior to similar duration CP in improving the sensorimotor recovery of patients with ischemic stroke at 90 days after enrollment. AyuRvedic TrEatment in the Rehabilitation of Ischemic STrOke Patients in India: A Randomized controllEd trial (RESTORE) is an investigator-initiated, multicenter, prospective, randomized, controlled, parallel-arm, blinded outcome assessment trial being conducted under the Indian Stroke Clinical Trial (INSTRuCT) Network across the four comprehensive stroke centers in India. Consecutive hemodynamically stable adult patients with their first acute ischemic stroke between 1 and 3 months from stroke onset are being randomized (1:1) into two treatment groups to receive either 1 month of ART or 1 month of CP. The primary outcome measure is the Fugl Meyer Assessment-upper extremity for physical performance at 90 days. The secondary outcomes are the modified Rankin Scale, Barthel Index, Berg Balance, and SF-36 at 90 days. The safety outcomes include a composite of irreversible morbidity and mortality. A sample size of 140 (70 in each group) patients with ischemic stroke will allow us to detect a minimal clinical important difference of 9.4 (standard deviation) with superiority margin of 5, an attrition rate of 10%, alpha of 5%, and power of 80%. This randomized trial will systematically assess the efficacy and safety of traditional ART compared to CP. The trial has been registered in the Clinical Trial Registry India (CTRI/2018/04/013379).

The untold saga of chromotherapy in dentistry.

Being a centuries-old concept and used successfully over years, chromotherapy is the method of treating diseases using coloured food, coloured clothing, colour saturated oils, coloured water and visible spectrum of electromagnetic radiation. The basis of chromotherapy depends on the fact that illness is caused by an imbalance in the basic chakras of the body. Colour therapy rebalances the chakras using specific colours. Being a part of complementary and alternative medicine systems, it proves to be effective for various systems of the body and affects neurohormonal pathways. Based on the available literature, this review documents the scientific evolution of colour therapy in medicine and dentistry and its various applications. Future studies will establish exactly how chromotherapy promotes wellbeing, owing to technical advancements and the scientific approach. Till then, it is a low-cost, non-invasive treatment option that is worth a go.

Immune status determined as per guidelines of Ayurveda found associated with clinical outcomes of COVID-19 disease - Results of a cross-sectional pilot study.

BACKGROUND: A key public health priority during the emergence of a novel pathogen is probing the factors contributing in clinical severity of the disease COVID-19. Moreover, analysis of the determined clinical outcomes is required and thus, modifiable predictor values need to identified. In Ayurveda, outcome of a disease is a multivariate function and this exploratory work is an attempt to identify one such factor "Vyadhiksamatwa" (immune status). MATERIALS AND METHODS: A questionnaire-based, cross-sectional study was conducted in fifty diagnosed cases of COVID-19. Study participants were subjected to a questionnaire to assess relationship between the three determinants of the disease - exposure, clinical severity, and Vyadhiksamatwa. RESULTS: Clinical severity was found strongly correlated with Vyadhiksmatwa with the value of Pearson Correlation - 0.740 significant at the 0.01 level (2-tailed). CONCLUSION: In the determination of clinical severity of disease, there are two epidemiological factors responsible - extrinsic (exposure) and intrinsic (Vyadhiksamatwa). It has been observed that higher the value of Vyadhiksamatwa of an individual, lesser will be the clinical severity of the disease in that individual. Vyadhiksamatwa can alter the host response to infections.

Phytochemistry, Pharmacology, and Toxicology of Datura Species-A Review.

Datura, a genus of medicinal herb from the Solanaceae family, is credited with toxic as well as medicinal properties. The different plant parts of Datura sp., mainly D. stramonium L., commonly known as Datura or Jimson Weed, exhibit potent analgesic, antiviral, anti-diarrheal, and anti-inflammatory activities, owing to the wide range of bioactive constituents. With these pharmacological activities, D. stramonium is potentially used to treat numerous human diseases, including ulcers, inflammation, wounds, rheumatism, gout, bruises and swellings, sciatica, fever, toothache, asthma, and bronchitis. The primary phytochemicals investigation on plant extract of Datura showed alkaloids, carbohydrates, cardiac glycosides, tannins, flavonoids, amino acids, and phenolic compounds. It also contains toxic tropane alkaloids, including atropine, scopolamine, and hyoscamine. Although some studies on D. stramonium have reported potential pharmacological effects, information about the toxicity remains almost uncertain. Moreover, the frequent abuse of D. stramonium for recreational purposes has led to toxic syndromes. Therefore, it becomes necessary to be aware of the toxic aspects and the potential risks accompanying its use. The present review aims to summarize the phytochemical composition and pharmacological and toxicological aspects of the plant Datura.

Yoga Therapy as an Adjuvant in Management of Asthma.

OBJECTIVE: To assess the effect of yoga on control of asthma in children with bronchial asthma. METHODS: This hospital-based interventional randomized controlled trial conducted in the Department of Pediatrics at a tertiary care center of North India from November 2017 to October 2018 enrolled 140 newly diagnosed cases of asthma of age 10-16 y who were randomly divided into two groups. Seventy children in the case group practiced yoga under supervision for a period of 3 mo in addition to pharmacological treatment. Seventy controls received only pharmacological treatment. Pulmonary-function tests were done at baseline, 6 wk, and 12 wk along with quality of life (QOL) assessment by Pediatric Asthma Quality of Life Questionnaire (PAQLQ). The outcome measures assessed were forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC and peak expiratory flow rate (PEFR). QOL evaluation was done in 3 domains: activity limitation, symptoms, and emotional function. RESULTS: The asthmatic children practicing yoga have shown significant improvement in FVC, FEV1, FEV1/FVC and PEFR which was better as compared to controls. Improvement was also noted in mean-PAQLQ score in cases which was statistically significantly better as compared to controls. CONCLUSION: Yoga appears to have significant positive effect on control of asthma measured by pulmonary-function test and QOL. Therefore yoga therapy can be recommended as an adjuvant in management of asthma along with standard pharmacological management.

Chemistry and Biology of Farnesol and its Derivatives: Quorum Sensing Molecules with Immense Therapeutic Potential.

BACKGROUND: Farnesol is an acyclic sesquiterpene alcohol, endogenously synthesized via the ergosterol pathway. It is a quorum sensing molecule (QSM) that was first discovered in C. albicans, and is involved in the inhibition of hyphae formation. METHODS: This review focuses on the comprehensive details of occurrence, chemical/biological synthesis of farnesol and its derivatives, and the factors involved in the regulation of their production. Further, the review also presents their cellular functions and diversified biomedical applications. RESULTS: Large-scale production of farnesol can be achieved using chemical synthesis and metabolic engineering approach. Farnesol is involved in the regulation of various physiological processes including filamentation, biofilm development, drug efflux, and apoptosis, etc. Farnesol and its derivatives/ analogues have also been reported to exhibit anti-biofilm, anti-cancer, anti-tumor and fungicidal properties. The antimicrobial potential of farnesol has been enhanced by synergizing it with known antifungal drugs, and also through nano-formulation(s). CONCLUSION: Apart from its quorum sensing activity, farnesol can be used as an effective anti-microbial, anti-inflammatory, ant-allergic, anti-cancerous, and anti-obesity agent.

An information, education and communication module to reduce dietary salt intake and blood pressure among tea garden workers of Assam.

OBJECTIVE: High salt diet increases blood pressure. Tea garden workers (TGW) of Assam, India have high (60.8%) prevalence of hypertension (HTN), which may be due to consumption of extra salt (salt as side dish) and salted tea at work place and home. The present study evaluated an information, education and communication (IEC) module to reduce salt intake and blood pressure among TGW. METHODS: Two tea gardens (usual care and intervention) were selected at random covering a total population of 13,458. The IEC module consisting of poster display, leaflets, health rally, documentary show, individual and group discussion was introduced in the intervention garden targeting study participants, health care providers, key stake holders, school children and teachers. IEC intervention was continued for one year. Participants from usual care and intervention were followed at three monthly intervals and BP and other information were compared after one year. RESULTS: A total of 393 study participants (Non intervention: 194; intervention: 199) were included. After one year of follow up, consumption of extra salt was reduced significantly in the intervention participants (66.3 vs. 45.5%, p=0.000). Intention to treat analysis revealed significant reduction in systolic [-6.4 (-8.6 to -4.2)] and diastolic [-6.9 (-8.1 to -5.7)] blood pressure after one year. Prevalence of HTN was reduced significantly (52.5 vs. 40.0%, p=0.02) among them. CONCLUSIONS: Our IEC module created awareness about risk of hypertension associated with high salt intake and could reduce dietary salt intake and BP.

Effect of green tea mouth rinse on Streptococcus mutans in plaque and saliva in children: An in vivo study.

AIMS: This study was conducted to evaluate and compare the antimicrobial efficacy of green tea catechin as a mouth wash on colony count of Streptococcus mutans in children. MATERIALS AND METHODS: A sample size of thirty children was selected out of screened 290 children by simple random sampling between the age group of 7 and 12 years. The study was conducted over a period of 2 weeks. After 24 h of oral prophylaxis, the baseline samples were collected and each group was subjected to mouth rinsing with green tea mouth wash for 2 weeks and further plaque and saliva samples were collected at 1- and 2-week intervals from baseline. Microbiological analysis of plaque and saliva samples was done by Dentocult SM strip kit (Orion Diagnostica, Finland), and the results were statistically analyzed and tabulated. RESULTS: Statistically, there was highly significant reduction in S. mutans count in plaque as well as in saliva for after 1- and 2-week intervals from baseline. CONCLUSION: Hence, finally, our study showed that green tea catechin is effective as a mouth wash against S. mutans and having better action in plaque as compared to saliva. It can be used as an adjunct to commercially available mouthwashes.

Phytotherapeutic Agents for Benign Prostatic Hyperplasia: An Overview.

BACKGROUND: Benign prostatic hyperplasia (BPH), the most common condition in aging men is the non cancerous proliferation of epithelial and stromal cells of the prostate gland and is associated with lower urinary tract symptoms (LUTS) such as frequency hesitancy urgency etc. Sources of symptoms in patient with BPH appear to be both static and dynamic component. Better understanding of the prostate physiology, function and pathogenesis has lead to the development of promising agents, useful in the management of lower urinary tract symptoms in men. OBJECTIVE: Treatment of clinical BPH aims to improve symptoms, prevent urinary tract infections, avoid renal insult, relief obstruction and improve bladder emptying. Many herbal formulations, or plant derived non-nutritive compounds with protective or disease preventive properties are getting popularized worldwide for the management of BPH, especially due to long term side effects of pharmacological treatment and risk of mortality associated with surgical procedures. Phytotherapeutic preparations are plant extracts with different components obtained by different extraction procedures. Numerous mechanisms of action have been postulated for mono and combination plant extracts. CONCLUSION: This article give a brief account of rationale and efficacy of various existing phytotherapeutic agents in the management of benign prostatic hyperplasia, including the herbs which hold the potential promise are also mentioned, although much research is still required.

Increased iron-stress resilience of maize through inoculation of siderophore-producing Arthrobacter globiformis from mine.

Iron deficiency is common among graminaceous crops. Ecologically successful wild grasses from iron-limiting habitats are likely to harbour bacteria which secrete efficient high-affinity iron-chelating molecules (siderophores) to solubilize and mobilize iron. Such siderophore-producing rhizobacteria may increase the iron-stress resilience of graminaceous crops. Considering this, 51 rhizobacterial isolates of Dichanthium annulatum from iron-limiting abandoned mine (∼84% biologically unavailable iron) were purified and tested for siderophore production; and efficacy of Arthrobacter globiformis inoculation to increase iron-stress resilience of maize and wheat was also evaluated. 16S rRNA sequence analyses demonstrated that siderophore-producing bacteria were taxonomically diverse (seven genera, nineteen species). Among these, Gram-positive Bacillus (eleven species) was prevalent (76.92%). A. globiformis, a commonly found rhizobacterium of graminaceous crops was investigated in detail. Its siderophore has high iron-chelation capacity (ICC: 13.0 ± 2.4 µM) and effectively dissolutes diverse iron-complexes (FeCl3 : 256.13 ± 26.56 µM/ml; Fe2 O3 red: 84.3 ± 4.74 µM/ml; mine spoil: 123.84 ± 4.38 µM/ml). Siderophore production (ICC) of A. globiformis BGDa404 also varied with supplementation of different iron complexes. In plant bioassay with iron-deficiency sensitive species maize, A. globiformis inoculation triggered stress-associated traits (peroxidase and proline) in roots, enhanced plant biomass, uptake of iron and phosphate, and protein and chlorophyll contents. However, in iron deficiency tolerant species wheat, growth improvement was marginal. The present study illustrates: (i) rhizosphere of D. annulatum colonizing abandoned mine as a "hotspot" of siderophore-producing bacteria; and (ii) potential of A. globiformis BGDa404 inoculation to increase iron-stress resilience in maize. A. globiformis BGDa404 has the potential to develop as bioinoculant to alleviate iron-stress in maize.

Prevalence of celiac disease in nutritional anemia at a tertiary care center.

BACKGROUND: While anemia occurs in 80 % to 90 % of patients with celiac disease (CD), it may be the sole manifestation of CD. The prevalence of CD in Indian patients with nutritional anemia is not known. PATIENTS AND METHODS: Adolescent and adult patients presenting with nutritional anemia were prospectively screened for CD using IgA anti-tissue transglutaminase antibody (anti-tTG Ab) followed, if positive, by upper gastrointestinal endoscopy and duodenal biopsy. RESULTS: Ninety-six patients [mean ± SD age 32.1 ± 13.1 years and median duration of anemia 11 months (range 1 to 144 months)] were screened. Of these patients, 80 had iron deficiency anemia, 11 had megaloblastic anemia, and 5 had dimorphic anemia. Seventy-three patients were on hematinics and 36.4 % had received blood transfusions. Nineteen had a history of chronic diarrhea and the mean ± SD duration of diarrhea in them was 9.7 ± 35.8 months. IgA anti-tTG Ab was positive in 13 patients, of whom 12 agreed to undergo duodenal biopsy. Ten patients had villous atrophy (Marsh grade 3a in three, 3b in one, and 3c in six) and two did not. Thus, 10 patients with nutritional anemia (iron deficiency 9, vitamin B12 deficiency 1) were diagnosed to have CD. On multivariate logistic regression, age, duration of symptoms, and presence of diarrhea were found to be the predictors of CD. All the patients with CD were put on gluten-free diet and with iron and vitamin supplementations and showed a significant improvement in hemoglobin concentration. CONCLUSIONS: CD screening should be included in the work up of otherwise unexplained nutritional anemia.

Antimycobacterial activity of Citrullus colocynthis (L.) Schrad. against drug sensitive and drug resistant Mycobacterium tuberculosis and MOTT clinical isolates.

ETHNOPHARMACOLOGICAL RELEVANCE: Citrullus colocynthis (Cucurbitaceae), a folk herbal medicine and traditionally used natural remedy for tuberculosis in India has been studied to validate its antitubercular activity against drug sensitive and drug resistant (including multidrug resistant) Mycobacterium tuberculosis and Mycobacterium other than tuberculosis (MOTT) bacilli. MATERIALS AND METHODS: Inhibitory and bactericidal activities of crude extracts, fractions and compounds of Citrullus colocynthis plant, consisting of aerial parts and ripe deseeded fruits were performed against the drug sensitive standard strain of Mycobacterium tuberculosis H37Rv (ATCC 27294), 16 drug resistant strains of Mycobacterium tuberculosis and two MOTT strains, using radiometric BACTEC 460TB system. RESULTS: Methanolic extract of ripe deseeded fruit of Citrullus colocynthis has shown good activity (MIC ≤ 62.5 µg/ml), whereas among the bioactive fractions, FC IX demonstrated the best activity (MIC 31.2 µg/ml) against Mycobacterium tuberculosis H37Rv. Bioactive FC III, IX and X also inhibited 16 clinical isolates of Mycobacterium tuberculosis consisting of seven non-multidrug resistants, eight multidrug resistants, one extensively drug resistant and two of MOTTs with MICs in the range of 50-125, 31.2-125 and 62.5-125 µg/ml, respectively. Ursolic acid and cucurbitacin E 2-0-ß-d-glucopyranoside were identified as the main biomarkers active against Mycobacterium tuberculosis H37Rv (MICs 50 and 25 µg/ml respectively), as well as against the 18 clinical isolates. FC III and FC IX showed better inhibition of drug resistant and MOTT clinical isolates. Minimal bactericidal concentrations of extracts, fractions and compound C-2 were ≥ two-fold MIC values. CONCLUSIONS: The study provides a scientific rationale for the traditional use of Citrullus colocynthis fruit in the treatment of tuberculosis. In addition, the study elucidates a broad spectrum antimycobacterial action of Citrullus colocynthis fruit, which can contribute to the development of improved preparation of an antitubercular natural drug for the treatment of drug resistant tuberculosis and MOTT infection as well.

Arrestin-dependent but G-protein coupled receptor kinase-independent uncoupling of D2-dopamine receptors.

We reconstituted D2 like dopamine receptor (D2R) and the delta opioid receptor (DOR) coupling to G-protein gated inwardly rectifying potassium channels (K(ir)3) and directly compared the effects of co-expression of G-protein coupled receptor kinase (GRK) and arrestin on agonist-dependent desensitization of the receptor response. We found, as described previously, that co-expression of a GRK and an arrestin synergistically increased the rate of agonist-dependent desensitization of DOR. In contrast, only arrestin expression was required to produce desensitization of D2R responses. Furthermore, arrestin-dependent GRK-independent desensitization of D2R-K(ir)3 coupling could be transferred to DOR by substituting the third cytoplasmic loop of DOR with that of D2R. The arrestin-dependent GRK-independent desensitization of D2R desensitization was inhibited by staurosporine treatment, and blocked by alanine substitution of putative protein kinase C phosphorylation sites in the third cytoplasmic loop of D2R. Finally, the D2R construct in which putative protein kinase C phosphorylation sites were mutated did not undergo significant agonist-dependent desensitization even after GRK co-expression, suggesting that GRK phosphorylation of D2R does not play an important role in uncoupling of the receptor.

Effects of fruit ellagitannin extracts, ellagic acid, and their colonic metabolite, urolithin A, on Wnt signaling.

Recent data suggest that ellagitannins (ETs), a class of hydrolyzable tannins found in some fruits and nuts, may have beneficial effects against colon cancer. In the stomach and gut, ETs hydrolyze to release ellagic acid (EA) and are converted by gut microbiota to urolithin A (UA; 3,8-dihydroxy-6H-dibenzopyran-6-one) type metabolites, which may persist in the colon through enterohepatic circulation. However, little is known about the mechanisms of action of either the native compounds or their metabolites on colon carcinogenesis. Components of Wnt signaling pathways are known to play a pivotal role in human colon carcinogenesis, and inappropriate activation of the signaling cascade is observed in 90% of colorectal cancers. This study investigated the effects of UA, EA, and ET-rich fruit extracts on Wnt signaling in a human 293T cell line using a luciferase reporter of canonical Wnt pathway-mediated transcriptional activation. The ET extracts were obtained from strawberry (Fragaria annassa), Jamun berry (Eugenia jambolana), and pomegranate (Punica granatum) fruit and were all standardized to phenolic content (as gallic acid equivalents, GAEs, by the Folin-Ciocalteu method) and to EA content (by high-performance liquid chromatography methods): strawberry = 20.5% GAE, 5.0% EA; Jamun berry = 20.5% GAE, 4.2% EA; pomegranate = 55% GAE, 3.5% EA. The ET extracts (IC(50) = 28.0-30.0 microg/mL), EA (IC(50) = 19.0 microg/mL; 63 microM), and UA (IC(50) = 9.0 microg/mL; 39 microM) inhibited Wnt signaling, suggesting that ET-rich foods have potential against colon carcinogenesis and that urolithins are relevant bioactive constituents in the colon.

Neuroprotective role of Convolvulus pluricaulis on aluminium induced neurotoxicity in rat brain.

AIM OF THE STUDY: Convolvulus pluricaulis (Convolvulaceae) has long been used as traditional herbal medicine in India as nerve tonic. We investigated neuroprotective effects of aqueous extract from Convolvulus pluricaulis (CP) against aluminium chloride induced neurotoxicity in rat cerebral cortex. MATERIAL, METHOD AND RESULT: Daily administration of CP (150 mg/kg) for 3 months along with aluminium chloride (50 mg/kg) decreased the elevated enzymatic activity of acetylcholine esterase and also inhibited the decline in Na(+)/K(+)ATPase activity which resulted from aluminium intake. Beside, preventing accumulation of lipid and protein damage, changes in the levels of endogenous antioxidant enzymes associated with aluminium administration were also rectified. Oral administration of CP preserved the mRNA levels of muscarinic receptor 1 (M1 receptor), choline acetyl transferase (ChAT) and Nerve Growth Factor-Tyrosine kinase A receptor (NGF-TrkA). It also ameliorated the upregulated protein expression of cyclin dependent kinase5 (Cdk5) induced by aluminium. The potential of CPE to inhibit aluminium induced toxicity was compared with rivastigmine tartrate (1mg/kg), which was taken as standard. The potential of the extract to prevent aluminium-induced neurotoxicity was also reflected at the microscopic level, indicative of its neuroprotective effects. CONCLUSION: Convolvulus pluricaulis possesses neuroprotective potential, thus validating its use in alleviating toxic effects of aluminium.

Inhibitory effect of novel diallyldisulfide analogs on HMG-CoA reductase expression in hypercholesterolemic rats: CREB as a potential upstream target.

AIMS: Diallyldisulfide (DADS), an active principle of garlic (Allium sativum) is known for its antihyperlipidemic properties. The present study was designed to evaluate the effect of novel synthesized DADS analogs, on the lipid profile of hypercholesterolemic rats and to investigate the molecular correlates of their activity at the cellular level. MAIN METHODS: Wistar rats, weighing 100-120 g each, were administered with 5% cholesterol for one week, and subsequently administered with lovastatin, allicin and DADS (20 mg/kg wt) analogs in the second week along with 5% cholesterol. All animals were sacrificed after overnight starvation. KEY FINDINGS: Our results show that DADS analogs are effective in reducing the total lipid levels which could be correlated with a significant decrease in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) activity. DADS analogs strongly inhibit HMGR activity in vivo but not in vitro. These results can be attributed to the significant decrease in the mRNA levels and protein expression of HMGR. Further, we show that DADS analogs significantly inhibited the activation of sterol regulatory element-binding protein-2 (SREBP-2) and interfered with DNA binding activity of cAMP response element-binding protein (CREB) but not nuclear factor-Y (NF-Y), with upstream regulatory sequences of HMGR. Moreover, DADS analogs are also effective in reducing the levels of oxidized low-density lipoprotein (ox-LDL), lipid peroxidation as well as NF-kappaB activity, showing good anti-inflammatory and antioxidant properties. SIGNIFICANCE: The unique anti-inflammatory effect and hypolipidemic action of DADS analogs may be beneficial in preventing the vascular complications that are induced by hyperlipidemia and provide a new therapeutic approach for the treatment of cardiovascular and related diseases.

The effect of the aqueous extract of the roots of Asparagus racemosus on hepatocarcinogenesis initiated by diethylnitrosamine.

Histopathological studies of the hepatic tissues of Wistar rats treated with diethylnitrosamine (DEN) (200 mg/kg b wt, i.p.) once a week for 2 weeks, followed by treatment with DDT, a tumor promoter (0.05% in diet) for 2 weeks and kept under observation for another 18 weeks, demonstrated the development of malignancy. Pretreatment of Wistar rats with the aqueous extract of the roots of Asparagus racemosus prevented the incidence of hepatocarcinogenesis. Immunohistochemical staining of the hepatic tissues of rats treated with DEN showed the presence of p53+ foci (clusters of cells expressing the mutated p53 protein), whereas an absence of p53+ foci was observed in Wistar rats pretreated with the aqueous extract of the roots of Asparagus racemosus. The microsections of the hepatic tissue of rats treated with DEN followed by treatment with the aqueous extract of Asparagus racemosus showed an absence of p53+ foci. The results of the biochemical determinations also show that pretreatment of Wistar rats with the aqueous extract of Asparagus racemosus leads to the amelioration of oxidative stress and hepatotoxicity brought about by treatment with DEN. These results prove that the aqueous extract of the roots of Asparagus racemosus has the potential to act as an effective formulation to prevent hepatocarcinogenesis induced by treatment with DEN.

Synthesis, DNA binding, and cytotoxic evaluation of new analogs of diallyldisulfide, an active principle of garlic.

Diallyldisulfide (DADS), an active principle of garlic (Allium sativum) is known for its antihyperlipidemic properties. However, its use is limited due to its extreme volatility. In the present study, we have synthesized and characterized a series of six new DADS analogs and investigated their interactions with different DNA duplexes. The spectroscopic and circular dichroism (CD) analyses revealed that DADS analogs bind preferentially with GC rich sequences. Thermodynamic parameters suggest that DADS analogs stabilize the calf thymus (CT) DNA and GC rich duplex by favorable enthalpic gains and follow the hierarchy, d(GC)(7)>CT DNA>d(AT)(10). Further, DADS analogs are less toxic and equally effective as the statins. The analogs therefore have a good potential to provide a new therapeutic approach for the treatment of cardiovascular and related diseases.