Indole-3 acetic acid induced cardiac hypertrophy in Wistar albino rats.

Indole-3-acetic acid (IAA) is the most widely utilized plant growth regulator. Despite its extensive usage, IAA is often overlooked as an environmental pollutant. Due to its protein-binding nature, it also functions as a uremic toxin, contributing to its association with chronic kidney disease (CKD). While in vitro and epidemiological research have demonstrated this association, the precise impact of IAA on cardiovascular disease in animal models is unknown. The main objective of this study is to conduct a mechanistic analysis of the cardiotoxic effects caused by IAA using male Wistar albino rats as the experimental model. Three different concentrations of IAA (125, 250, 500 mg/kg) were administered for 28 days. The circulating IAA concentration mimicked previously observed levels in CKD patients. The administration of IAA led to a notable augmentation in heart size and heart-to-body weight ratio, indicating cardiac hypertrophy. Echocardiographic assessments supported these observations, revealing myocardial thickening. Biochemical and gene expression analyses further corroborated the cardiotoxic effects of IAA. Dyslipidemia, increased serum c-Troponin-I levels, decreased SOD and CAT levels, and elevated lipid peroxidation in cardiac tissue were identified. Moreover, increased expression of cardiac inflammatory biomarkers, including ANP, BNP, ß-MHC, Col-III, TNF-α, and NF-κB, was also found in the IAA-treated animals. Histopathological analysis confirmed the cardiotoxic nature of IAA, providing additional evidence of its adverse effects on cardiovascular health. These results offer insights into the potential negative impact of IAA on cardiovascular function, and elucidating the underlying mechanisms of its cardiotoxicity.

Altered cerebellar lobular volumes correlate with clinical deficits in siblings and children with ASD: evidence from toddlers.

BACKGROUND: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impaired social and communication skills, narrow interests, and repetitive behavior. It is known that the cerebellum plays a vital role in controlling movement and gait posture. However, recently, researchers have reported that the cerebellum may also be responsible for other functions, such as social cognition, reward, anxiety, language, and executive functions. METHODS: In this study, we ascertained volumetric differences from cerebellar lobular analysis from children with ASD, ASD siblings, and typically developing healthy controls. In this cross-sectional study, a total of 30 children were recruited, including children with ASD (N = 15; mean age = 27.67 ± 5.1 months), ASD siblings (N = 6; mean age = 17.5 ± 3.79 months), and typically developing children (N = 9; mean age = 17.67 ± 3.21 months). All the MRI data was acquired under natural sleep without using any sedative medication. We performed a correlation analysis with volumetric data and developmental and behavioral measures obtained from these children. Two-way ANOVA and Pearson correlation was performed for statistical data analysis. RESULTS: We observed intriguing findings from this study, including significantly increased gray matter lobular volumes in multiple cerebellar regions including; vermis, left and right lobule I-V, right CrusII, and right VIIb and VIIIb, respectively, in children with ASD, compared to typically developing healthy controls and ASD siblings. Multiple cerebellar lobular volumes were also significantly correlated with social quotient, cognition, language, and motor scores with children with ASD, ASD siblings, and healthy controls, respectively. CONCLUSIONS: This research finding helps us understand the neurobiology of ASD and ASD-siblings, and critically advances current knowledge about the cerebellar role in ASD. However, results need to be replicated for a larger cohort from longitudinal research study in future.

Phytonutrient Inhibitors of SARS-CoV-2/NSP5-Encoded Main Protease (Mpro) Autocleavage Enzyme Critical for COVID-19 Pathogenesis.

The genomic reshuffling, mutagenicity, and high transmission rate of the SARS-CoV-2 pathogen highlights an urgent need for effective antiviral interventions for COVID-19 control. Targeting the highly conserved viral genes and/or gene-encoded viral proteins such as main proteinase (Mpro), RNA-dependent RNA polymerase (RdRp) and helicases are plausible antiviral approaches to prevent replication and propagation of the SARS-CoV-2 infection. Coronaviruses (CoVs) are prone to extensive mutagenesis; however, any genetic alteration to its highly conserved Mpro enzyme is often detrimental to the viral pathogen. Therefore, inhibitors that target the Mpro enzyme could reduce the risk of mutation-mediated drug resistance and provide effective antiviral protection. Several existing antiviral drugs and dietary bioactives are currently repurposed to treat COVID-19. Dietary bioactives from three ayurvedic medicinal herbs, 18 ß-glycyrrhetinic acid (ΔG = 8.86 kcal/mol), Solanocapsine (ΔG = 8.59 kcal/mol), and Vasicoline (ΔG = 7.34 kcal/mol), showed high-affinity binding to Mpro enzyme than the native N3 inhibitor (ΔG = 5.41 kcal/mol). Flavonoids strongly inhibited SARS-CoV-2 Mpro with comparable or higher potency than the antiviral drug, remdesivir. Several tannin hydrolysates avidly bound to the receptor-binding domain and catalytic dyad (His41 and Cys145) of SARS-CoV-2 Mpro through H-bonding forces. Quercetin binding to Mpro altered the thermostability of the viral protein through redox-based mechanism and inhibited the viral enzymatic activity. Interaction of quercetin-derivatives with the Mpro seem to be influenced by the 7-OH group and the acetoxylation of sugar moiety on the ligand molecule. Based on pharmacokinetic and ADMET profiles, several phytonutrients could serve as a promising redox nutraceutical for COVID-19 management.

Automatic Classification of Healthy Subjects and Patients With Essential Vocal Tremor Using Probabilistic Source-Filter Model Based Noise Robust Pitch Estimation.

Essential voice tremor (EVT) is a voice disorder resulting from dyscoordination within the laryngeal musculature. A low-frequency fluctuations of fundamental voice frequency or the strength of excitation amplitude is the main consequence of the disorder. The automatic classification of healthy control and EVT is useful tool for the clinicians. A typical automatic EVT classification involves three steps. The first step is to compute the pitch contour from the speech. The second step is to compute the features from the pitch contour, and the final step is to use a classifier to classify the features into healthy or EVT. It is shown that a high-resolution pitch contour estimated from the glottal closure instants (GCIs) is useful for EVT classification. The HPRC estimation can be very poor in the presence of noise. Hence, a probabilistic source filter model based noise robust GCI detection is used for HPRC estimation. The Empirical mode decomposition based feature extraction is used followed by a support vector machine classifier. The EVT classification performance is evaluated using recordings from 45 subjects. The proposed method is found to perform better than the baseline techniques in eight different additive noise conditions with six SNR levels.

Methylenetetrahydrofolate reductase polymorphisms in dental caries-induced pulp inflammation and regeneration of dentine-pulp complex: Future perspectives.

Dental caries (DC)-induced pulp infections usually undergo the common endodontic treatment, root canal therapy (RCT). Endodontically treated teeth are devitalized, become brittle and susceptible for re-infection which eventually results in dental loss. These complications arise because the devitalized pulp losses its ability for innate homeostasis, repair and regeneration. Therefore, restoring the vitality, structure and function of the inflamed pulp and compromised dentin have become the focal points in regenerative endodontics. There are very few evidences, so far, that connect methylenetetrahydrofolate reductase single nucleotide polymorphisms (MTHFR-SNPs) and dental disorders. However, the primary consequences of MTHFR-SNPs, in terms of excessive homocysteine and folate deficiency, are well-known contributors to dental diseases. This article identifies the possible mechanisms by which MTHFR-SNP-carriers are susceptible for DC-induced pulp inflammation (PI); and discusses a cell-homing based strategy for in vivo transplantation in an orthotopic model to regenerate the functional dentine-pulp complex which includes dentinogenesis, neurogenesis and vasculogenesis, in the SNP-carriers.

Assessment of Voice Outcomes Post Chemo-Radiotherapy in Non-Laryngeal Head & Neck Cancers Using Electroglottography and Voice Symptom Scale (VoiSS) Questionnaire.

BACKGROUND: Laryngeal toxicity (LT) following concurrent chemo-radiotherapy (CCRT) for non-laryngeal head & neck cancers(NLHNC) has been inadequately studied. Electroglottography (EGG), a non-invasive technique for objective quantification of LT, measures the change in electrical impedance generated by glottic closure. AIM: Objective and subjective assessment of acute LT post-CCRT in NLHNC. MATERIALS AND METHODS: A prospective study on 30 NLHNC patients, treated with CCRT; 66-70Gy/33- 35fractions with weekly Cisplatin. Flexible laryngoscopic examination and EGG were performed at baseline, 6weeks, and 3months post-CCRT; Grades of LT and contact quotients(CQ) were documented. Patientreported outcomes of voice-related quality of life(QoL) performed at the same intervals, using a 30-item Voice Symptom Scale (VoiSS) questionnaire. STATISTICAL ANALYSIS: Results of continuous measurements were studied by mean +/- standard deviation. Analysis of variance (ANOVA) was used for comparison of pretreatment and post-treatment results in more than two groups. Significance was assessed at 5% level ofsignificance. Post- hoc analysis has been done using Tukey-Krammer method for multiple comparisons. Correlation analysis was performed using Pearson correlation test. RESULTS: 26/30 patients completed CCRT; 14 were available at 6weeks; 10 at 3months post-CCRT for analysis. At 6 weeks, 3/14(21.5%) patients had Grade II LT; 11/14(78.57%) had grade III. At 3months, 2/10(20%) had Grade I, 6/10(60%) had grade II but 2/10(20%) had worsened to grade IV. Mean CQ at baseline was 50.77 +/- 5.55; which decreased at 6 weeks to 48.56 +/- 4.66 and further at 3months to 45.56 +/- 4.66 (>0.05) suggestive of glottic hypo-adduction. VoiSS responses showed a significant impact on QoL in all three domains at six weeks and three months post-CCRT, compared to baseline (P < 0.0001). CONCLUSION: Electroglottography is a potential tool to quantify acute LT post CCRT. Patient-reported outcomes may not correlate to the objective measures of laryngeal toxicity and require separate recording and reporting. A larger sample size would be required to draw further significant correlations. Key Words: Electroglottography; laryngeal toxicity; head neck cancer; voice; chemo-radiotherapy.

The association of ABO blood group with the asymptomatic COVID-19 cases in India

The COVID-19 pandemic has resulted several waves of infection in many countries worldwide. The large variations in case fatality ratio among different geographical regions suggests that the human susceptibility against this virus varies substantially. Several studies from different parts of the world showed a significant association of ABO blood group and COVID-19 susceptibility. It was shown that individuals with blood group O are at the lower risk of coronavirus infection. To establish the association of ABO blood group in SARS-CoV-2 susceptibility, we for the first time analysed SARS-CoV-2 neutralising antibodies as well as blood groups among 509 random individuals from three major districts of Eastern Uttar Pradesh region of India.. Interestingly, we found neutralising antibodies in significantly higher percentage of people with blood group AB (0.36) followed by B (0.31), A (0.22) and lowest in people with blood group O (0.11). This indicates that people with blood group AB are at comparatively higher risk of infection than other blood groups. Further, in line to previous reports we too observed that people with blood group O have significantly decreased risk of SARS-CoV-2 infection. Thus, among the asymptomatic SARS-CoV-2 infected individuals with blood group AB has highest, whilst blood group O has lowest risk of infection.

Estimation of real-infection and immunity against SARS-CoV-2 in Indian populations

Infection born by Coronavirus SARS-CoV-2 has swept the world within a time of a few months. It has created a devastating effect on humanity with social and economic depression. Europe and America were the hardest hit continents. India has also lost lives, making the country fourth most deadly worldwide. However, the infection and death rate per million and the case fatality ratio in India were substantially lower than in many developed nations. Several factors have been proposed including genetics. One of the important facts is that a large chunk of Indian population is asymptomatic to the SARS-CoV-2 infection. Thus, the real infection in India is much higher than the reported number of cases. Therefore, the majority of people are already immune in the country. To understand the dynamics of real infection as well as the level of immunity against SARS-CoV-2, we have performed antibody testing (serosurveillance) in the urban region of fourteen Indian districts encompassing six states. In our survey, the seroprevalence frequency varied between 0.01-0.48, suggesting high variability of viral transmission between states. We also found out that the cases reported by the government were several fold lower than the real incidence of infection. This discrepancy is mainly driven by the higher number of asymptomatic cases. Overall, we suggest that with the high level of immunity developed against SARS-CoV-2 in the majority of the districts, the case fatality rate of second wave in India will be minor than first wave.

Emerging behavioral and neuroimaging biomarkers for early and accurate characterization of autism spectrum disorders: a systematic review.

The possibility of early treatment and a better outcome is the direct product of early identification and characterization of any pathological condition. Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social communication, restricted, and repetitive patterns of behavior. In recent times, various tools and methods have been developed for the early identification and characterization of ASD features as early as 6 months of age. Thorough and exhaustive research has been done to identify biomarkers in ASD using noninvasive neuroimaging and various molecular methods. By employing advanced assessment tools such as MRI and behavioral assessment methods for accurate characterization of the ASD features and may facilitate pre-emptive interventional and targeted therapy programs. However, the application of advanced quantitative MRI methods is still confined to investigational/laboratory settings, and the clinical implication of these imaging methods in personalized medicine is still in infancy. Longitudinal research studies in neurodevelopmental disorders are the need of the hour for accurate characterization of brain-behavioral changes that could be monitored over a period of time. These findings would be more reliable and consistent with translating into the clinics. This review article aims to focus on the recent advancement of early biomarkers for the characterization of ASD features at a younger age using behavioral and quantitative MRI methods.

Antioxidant and Antiapoptotic effect of aqueous extract of Pueraria tuberosa (Roxb. Ex Willd.) DC. On streptozotocin-induced diabetic nephropathy in rats.

BACKGROUND: Oxidative stress and renal apoptosis play a significant role in the progression of diabetic nephropathy. The tubers of Pueraria tuberosa (Roxb. ex Willd.) DC. has been traditionally used as anti-ageing and health promotive tonic. The purpose of this study was to investigate its nephroprotective effect and mechanism via antioxidant and antiapoptotic potential in Streptozotocin-induced diabetic nephropathy (DN) in rats. METHODS: The chemical composition of aqueous extract of Pueraria tuberosa (PTY-2r) was analyzed by gas chromatography-mass spectrometry (GC-MS). Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) (55 mg/kg body weight) in rats. After 60 days, the rats were randomly divided into 3 groups (n = 6/each group), namely DN control (DN) group-2, DN rats treated with PTY-2r at the dose of 50 mg/100 g, group-3 and 100 mg/100 g, group-4 p.o. for 20 days. The normal rats were chosen as a normal control (NC) group-1. PTY-2r was orally given to the rats for 20 days. Reactive oxygen species (ROS), lipid peroxidation (LPO) and the activity of ROS-scavenging enzymes - superoxide dismutase (SOD), catalase (CAT) & glutathione peroxidase (GPx) were determined in the kidney tissue of DN rats. The expression of apoptosis-related proteins was measured by immunofluorescence. RESULTS: GC-MS analysis of PTY-2r indicated the presence of 37 compounds among them 5-Hydroxymethylfurfural (17.80%), 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (17.03%), n-Hexadecanoic acid (5.18%) and 9-Octadecenoic acid (Z) - (6.69%) were found in the higher amount. A significant increase in ROS and LPO was observed along with the decreased activity of antioxidant enzymes, responsible for oxidative stress in the kidney of DN rats. Since, high oxidative stress induces apoptosis in target cells, as shown by significantly decreased expression of Bcl-2 along with increased expression of Bax, active Caspase-3 & cleaved PARP-1 in DN control rats, suggesting apoptosis. The PTY-2r treatment significantly raised the activity of antioxidant enzymes, suppressed oxidative stress and apoptosis thus, prevented urinary albumin excretion in a dose-dependent manner. CONCLUSIONS: The findings suggest that PTY-2r exerted the nephroprotective potential against STZ induced DN rats via suppressing oxidative stress and apoptosis due to the presence of different bioactive compounds. ᅟ.

Pueraria tuberosa extract inhibits iNOS and IL-6 through suppression of PKC-α and NF-kB pathway in diabetes-induced nephropathy.

OBJECTIVES: Inflammation plays an important role in the pathogenesis of diabetic nephropathy (DN). The aim of this study was to explore the anti-inflammatory role of PTY-2r (extracted from Pueraria tuberosa), on streptozotocin (STZ)-induced DN rats. METHODS: Diabetes was induced by intraperitoneal injection of STZ (55mg/kg) in rats. After 60 days, the rats were randomly divided into three groups (n = 6/each group), namely DN control group 2, DN rats treated with PTY-2r at dose of 100 mg/100 g, group 3 and 50 mg/100 g, group 4, p.o for 20 days. The normal rats were chosen as a normal control (NC) group 1. KEY FINDINGS: In DN rats, the expression of iNOS and inflammatory cytokines (IL-6 and TNF-α) was significantly increased. Raised expression of PKC-α was also found. As NF-kB is the main transcription factor for the inflammatory response-mediated progression of DN, variation in NF-kB expression and its activated phosphorylated derivative (pNF-kB) were also evaluated and increase in expression was obtained in the kidney of DN rats. PTY-2r treatment significantly reversed these changes in dose-dependent manner. CONCLUSIONS: This study suggested that the nephroprotective effect of PTY-2r is possibly due to downregulation of PKC-α and NF-kB pathway and normalizing the expression of inflammatory cytokines and iNOS in the kidney of DN rats.

Effect of extract of Pueraria tuberosa on expression of hypoxia inducible factor-1α and vascular endothelial growth factor in kidney of diabetic rats.

BACKGROUNDS: Kidney hypoxia represents a unifying mechanism in the pathogenesis of diabetic nephropathy. Hypoxia-induced factor (HIF)-1α mediates the metabolic responses of renal hypoxia by modulating the expression of VEGF. In the present study, we investigated the effect of Pueraria tuberosa extract (PTY-2r) on the expression of HIF-1α, VEGF and nephrin in streptozotocin (STZ) induced diabetic nephropathy (DN). METHODS: The model of diabetic nephropathy (DN) was produced by intraperitoneal injection of 55mg/kg of STZ and maintained for 60days. These DN-rats were randomly divided into three groups, i.e., DN, DN+PTY-2r (100mg/100g), and DN+PTY-2r (50mg/100g). A normal control (NC) group was administrated with drug vehicle. Expression of HIF-1α, VEGF and nephrin were evaluated in the renal tissue. RESULTS: Blood glucose, urine protein, serum creatinine, and urea, level were significantly raised along with decreased creatinine clearance in DN rats. Immunofluorescence and Western blot analysis showed significantly increased expression of HIF-1α & VEGF and decreased expression of nephrin in DN control rats. The PTY-2r treatment significantly reversed these changes in a dose-dependent manner. Correlation analysis showed that the expression of VEGF was positively correlated with that of HIF-1α and negatively correlated with nephrin. CONCLUSIONS: The PTY-2r can improve the chronic hyperglycemic condition induced kidney damage, and may delay the development of diabetic nephropathy by inhibiting the expression of HIF-1α and VEGF, thereby restoring the expression of nephrin.

Acoustic analysis of voice in nonlaryngeal head and neck cancer patients post chemoradiotherapy.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) used for definitive management of locally advanced head and neck squamous cell carcinoma (HNSCC) allows organ preservation at the cost of preservation of function. Vocal cords, being within the field of irradiation, undergo acute and chronic changes which adversely impacts the patients' voice. AIMS: To assess the acute changes in the acoustic characteristics of voice post-CCRT in patients with nonlaryngeal HNSCC. MATERIALS AND METHODS: Thirty patients with HNSCC treated with CCRT, a total dose of 66-70 Gy/33-35 fractions at five fractions/week, with weekly cisplatin. Acoustic analysis (AA) and laryngoscopic examination performed at baseline, 6 weeks, and 3 months post-CCRT. Statistical analysis of the parameters using ANOVA and Student's t-test was performed. RESULTS: Of the thirty patients, 26 patients completed CCRT. At 6 weeks post-CCRT, among 14/26 patients, most (11/14 [78.57%]) developed Grade III toxicity. On AA, both increase and decrease in mean F0 from baseline was observed. An increase (P < 0.05) in each, i.e., jitter, shimmer, and noise to harmonics ratio (NHR) were recorded. At 3 months post-CCRT, among 8/14 available, most (6/8 [75%]) showed Grade II toxicity. The mean F0 reduced for both genders; jitter and shimmer, and NHR values maintained an increase (P > 0.05). CONCLUSIONS: Periodic AA allows quantification of voice changes and mapping of vocal toxicity induced by CCRT.

An extract of Pueraria tuberosa tubers attenuates diabetic nephropathy by upregulating matrix metalloproteinase-9 expression in the kidney of diabetic rats.

BACKGROUND: Currently, no drug is available to directly target the signaling molecules involved in the pathogenesis of diabetic nephropathy (DN); only antihypertensive and antidiabetic drugs are in clinical use. In the present study, the therapeutic effects of a active fraction of tubers from Pueraria tuberosa (hereafter referred to as PTY-2) were investigated in streptozotocin (STZ)-diabetic rats with DN, with particular emphasis on its effects on extracellular matrix (ECM) accumulation and matrix metalloproteinase (Mmp)-9 expression in kidney tissue. METHODS: Rats were injected with 55 mg/kg, i.p., STZ. After 40 days, rats were divided into groups as follows (n = 6 per group): Group 1, age-matched rats not injected with STZ (non-diabetic control); Group 2, STZ-diabetic DN rats; and Group 3, PTY-2 (30 mg/100 g, p.o.)-treated DN rats. After 20 days treatment, the effects of PTY-2 on serum urea and creatinine concentrations, urinary levels of glucose, creatinine, protein, and ketone bodies, and urine pH were determined. Kidney tissue was evaluated for Mmp-9 expression and histological changes. RESULTS: Blood glucose, serum urea, creatinine, and urine protein levels were significantly higher, and creatinine clearance was significantly lower, in Group 2 versus Group 1 rats. There was a higher degree of glomerulosclerosis, expansion of the mesangial matrix, and excess ECM deposition and eosinophilic casts in kidneys from Group 2 versus Group 1 rats. Furthermore, Mmp-9 activity and expression were significantly reduced in kidney homogenate of Group 2 versus Group 1 rats. Interestingly, PTY-2 treatment significantly reversed all these changes in DN rats. CONCLUSION: Treatment of DN rats with PTY-2 significantly attenuated the severity of DN by increasing the expression and activity of Mmp-9, consequently degrading the ECM accumulated in kidney tissue.

Nfkb1 is a haploinsufficient DNA damage-specific tumor suppressor.

NF-κB proteins play a central and subunit-specific role in the response to DNA damage. Previous work identified p50/NF-κB1 as being necessary for cytotoxicity in response to DNA alkylation damage. Given the importance of damage-induced cell death for the maintenance of genomic stability, we examined whether Nfkb1 acts as a tumor suppressor in the setting of alkylation damage. Hprt mutation analysis demonstrates that Nfkb1(-/-) cells accumulate more alkylator-induced, but not ionizing radiation (IR)-induced, mutations than similarly treated wild-type cells. Subsequent in vivo tumor induction studies reveal that following alkylator treatment, but not IR, Nfkb1(-/-) mice develop more lymphomas than similarly treated Nfkb1(+/+) animals. Heterozygous mice develop lymphomas at an intermediate rate and retain functional p50 in their tumors, indicating that Nfkb1 acts in a haploinsufficient manner. Analysis of human cancers, including therapy-related myeloid neoplasms, demonstrates that NFKB1 mRNA expression is downregulated compared with control samples in multiple hematological malignancies. These data indicate that Nfkb1 is a haploinsufficient, pathway-specific tumor suppressor that prevents the development of hematologic malignancy in the setting of alkylation damage.

Antioxidant capacity and radical scavenging effect of polyphenol rich Mallotus philippenensis fruit extract on human erythrocytes: an in vitro study.

Mallotus philippinensis is an important source of molecules with strong antioxidant activity widely used medicinal plant. Previous studies have highlighted their anticestodal, antibacterial, wound healing activities, and so forth. So, present investigation was designed to evaluate the total antioxidant activity and radical scavenging effect of 50% ethanol fruit glandular hair extract (MPE) and its role on Human Erythrocytes. MPE was tested for phytochemical test followed by its HPLC analysis. Standard antioxidant assays like DPPH, ABTS, hydroxyl, superoxide radical, nitric oxide, and lipid peroxidation assay were determined along with total phenolic and flavonoids content. Results showed that MPE contains the presence of various phytochemicals, with high total phenolic and flavonoid content. HPLC analysis showed the presence of rottlerin, a polyphenolic compound in a very rich quantity. MPE exhibits significant strong scavenging activity on DPPH and ABTS assay. Reducing power showed dose dependent increase in concentration absorption compared to standard, Quercetin. Superoxide, hydroxyl radical, lipid peroxidation, nitric oxide assay showed a comparable scavenging activity compared to its standard. Our finding further provides evidence that Mallotus fruit extract is a potential natural source of antioxidants which have a protective role on human Erythrocytes exhibiting minimum hemolytic activity and this justified its uses in folklore medicines.

Hepatic encephalopathy: cause and possible management with botanicals.

Hepatic encephalopathy is a brain functional disorder, characterized by neuropsychiatric abnormalities with liver failure. High blood ammonia, causing glutamate neurotoxicity is the basic cause, finally leading to low-grade cerebral edema. Its manifestation is more likely in patients of sepsis, oxidative stress, generalized inflammation, gut mal-functioning, amoebiaesis, viral hepatitis, nervous imbalance, etc. Thus, the therapeutic goals primarily include the maintenance of proper blood supply and prevention of hypoxic condition in liver, along with management of factors responsible for high blood ammonia, oxidative stress, inflammation, and high GI- serotonin. The drugs in clinical practice include lactulose, sodium benzoate, flumazenil and rifaximin, supplementation of zinc, branched chain amino acids (BCAA), l-ornithine-l aspartate, antioxidants and iNOS inhibitors. However, herbal formulations would be of great importance as it shows multi-targeted action because it possesses a natural cocktail of secondary metabolites. It can collectively act as an antioxidant, anti-inflammatory, prebiotic, hepatoprotective and neuron-protective agents. We have briefly outlined some of these plants and also recent patents useful in the management of hepatic encephalopathy.

Insulin secreting and alpha-glucosidase inhibitory activity of hexane extract of Annona squamosa Linn. in streptozotocin (STZ) induced diabetic rats.

The hexane extract of A. squamosa (ASHE) in 100 and 400 mg/kg body weight dose raised the insulin level when compared with Glimepiride (1 mg/kg) and also inhibited alpha-glucosidase activity when compared with Acarbose (10 mg/kg) in streptozotocin induced diabetic rats. The ASHE significantly reduced peak blood glucose (Gp30) and area under curve (AUC) in diabetic rats in oral glucose (OGTT) and oral sucrose (OSTT) tolerance test, but there was more reduction of Gp30 value than AUC in OSTT. Thus, it can be suggested that the ASHE, has hypoglycemic role at 2 levels, i.e. it acts as secretagogue and also inhibits the intestinal enzymes, responsible for glucose metabolism.

Enhanced antilipopolysaccharide (LPS) induced changes in macrophage functions by Rubia cordifolia (RC) embedded with Au nanoparticles.

In this paper, we have shown that gold nanoparticles (Au (NPs)) embedded in Rubia cordifolia (RC) matrix (RC-Au (NPs)) exhibit a high therapeutic value relating to its anti-inflammatory characteristics. It was prepared by utilizing the reducing properties of RC to convert HAuCl4 into Au (NPs). In order to compare its effectiveness, with respect to Au (NPs), the latter was synthesized separately by reducing HAuCl4 with lemon extract. These Au (NPs) along with RC-Au (NPs) were characterized by X-ray diffractometry (XRD), transmission electron microscopy (TEM), and UV-visible spectroscopy. The enhancement in anti-inflammatory characteristics was assessed as its inhibitory potential for lipopolysaccharide (LPS)-induced nitric oxide (NO) release, by rat peritoneal macrophages. The RC-Au (NPs) significantly enhanced its potential to inhibit NO release, which was reported in terms of inhibitory concentration for 50% inhibition (IC50=11.98 ng/ml), as compared to either RC extract (IC50=47 × 10(3)ng/ml) or to Au (NPs) (IC50=587.50 ng/ml).

Anti-inflammatory effect of Pueraria tuberosa extracts through improvement in activity of red blood cell anti-oxidant enzymes.

Changing life style and over-nutrition causes low-grade inflammation (LGI), with obesity and hyper-lipidemia as basic factors. The physiological state polarizes macrophages to classical type (M1), which is pro-inflammatory and promotes ectopic fat deposition in the body. Both factors induce inflammatory cascade, where free radicals (FRs) play an important role. Thus, pharmacological and non-pharmacological interventions would be effective in the management of LGI and plant products would be used as food supplement or as a drug. Previously, a study has reported the anti-oxidant potential of methanolic extract of tubers of Pueraria tuberosa (PTME) and inhibitory role of tuberosin on lipopolysaccharides-induced expression of inducible nitric oxide synthase in macrophages in an in vitro study model. Here, the effect of PTME has been explored on carrageenan-induced inflammatory changes in rats. The activity of antioxidant enzymes in red blood cell hemolysate has been assessed. PTME was orally given to rats for 9 days and periodical changes (every 3(rd) day) in the activity/concentration of superoxide dismutase (SOD), catalase, reduced glutathione (GSH), lipid peroxides (LPO), and C-reactive proteins (CRP) were monitored. The PTME significantly prevented carrageenan-induced decline in GSH content, lowering of catalase and SOD activity, and rise in LPO and CRP in rats in a time-dependent, sequential manner. Thus, it could be suggested that the anti-inflammatory role of PTME is primarily mediated through its FR scavenging potential.