Immunomodulatory Effect of Gymnema sylvestre (R.Br.) Leaf Extract: An In Vitro Study in Rat Model

Gymnema sylvestre Wild R.Br (family: Asclepidaceae) is a valuable medicinal plant used in folk medicine to treat diabetes, obesity, asthma etc. in India for antiquity. Diabetes mellitus is a syndrome characterized immunologically by lymphocyte apoptosis and reduced cell-mediated and humoral immunity. Modulation of immune responses to alleviate diseases has been of interest, and traditional herbal medicines may play an important role in this regard. In this study, we aim to evaluate the immunomodulatory potential of methanolic extract of G. sylvestre leaf using rat model. HPLC analysis of leaf extract was carried out for gymnemic acid. The method involves the initial hydrolysis of gymnemic acids, the active ingredients, to a common aglycone followed by the quantitative estimation of gymnemagenin, using gymnemagenin as reference standard. Gymnemic acid content was 2.40% (w/w) in G. sylvestre leaf extract. In vitro immunomodulatory activity of the methanolic extract of G. sylvestre leaf (1–200μg/ml) was evaluated by gauging its effects on nitroblue tetrazolium reduction and nitrite release in rat peritoneal macrophages and on mitogen (ConA, PHA and LPS) induced splenic lymphocyte proliferation. G. sylvestre leaf extract showed significant (<0.05) enhancement in NO and ROS generation in macrophages and in proliferation of lymphocytes in dose dependent manner. EC₅₀ value was 3.10, 3.75 and 2.68μg/ml for NBT reduction, nitrite release and lymphoproliferation, respectively. Potential effect was observed at 100 μg/ml in NO and ROS generation in macrophages and 20 μg/ml in lymphocyte proliferation. G. sylvestre leaf extract stimulates macrophage reactivity, increasing the level of activity even higher when combined with PMA or LPS. These findings suggest the presence of active compounds, gymnemic acid, in methanolic extract of G. sylvestre leaf that stimulates both myeloid and lymphoid components of immune system, and therefore can restore the innate immune function. Through this study, the traditional knowledge of anti-diabetic property of G. sylvestre is scientifically supplemented with its immunomodulatory properties.     

Modulation of osmotic stress effects on photosynthesis and respiration by temperature in mesophyll protoplast of pea

Exposure of mesophyll protoplast of pea to osmotic stress decreases the rate of photosynthesis while stimulating marginally the respiratory rate of mesophyll protoplasts. The interaction of osmotic and temperature stress during the modulation of photosynthetic and respiratory rates of pea (Pisum sativum var Azad P1) mesophyll protoplasts was investigated. The protoplasts were exposed to either iso-osmotic (0.4 M) or hyper-osmotic (1.0 M) concentration of sorbitol at 15 degrees and 25 degrees C. The rates of photosynthesis and respiration were studied. At optimum temperature of 25 degrees C, there was a decrease in photosynthesis (< 10%) at hyper-osmoticum (osmotic effect), whereas respiration increased marginally (by about 15%). Low temperature (15 degrees C) aggravated the sensitivity of both respiration and photosynthesis to osmotic stress. At 15 degrees C, the decrease in photosynthesis due to osmotic stress was > 35%, while the respiratory rate was stimulated by 30%. The relative proportion of cytochrome pathway decreased by about 50% at both 15 degrees C and 25 degrees C while that of alternative pathway increased, more so, at 15 degrees C, when the mesophyll protoplasts were subjected to hyper-osmoticum stress. The titration experiments showed that extent of engagement of alternative pathway was higher, the slope value was slightly higher for 15 degrees C compared to 25 degrees C. Low temperature modulates the effect of hyper-osmoticum stress on photosynthesis and respiration, and results in increased participation of alternative pathway.     

Hippocampal chromatin‐modifying enzymes are pivotal for scopolamine‐induced synaptic plasticity gene expression changes and memory impairment

The amnesic potential of scopolamine is well manifested through synaptic plasticity gene expression changes and behavioral paradigms of memory impairment. However, the underlying mechanism remains obscure and consequently ideal therapeutic target is lacking. In this context, chromatin‐modifying enzymes, which regulate memory gene expression changes, deserve major attention. Therefore, we analyzed the expression of chromatin‐modifying enzymes and recovery potential of enzyme modulators in scopolamine‐induced amnesia. Scopolamine administration drastically up‐regulated DNA methyltransferases (DNMT1) and HDAC2 expression while CREB‐binding protein (CBP), DNMT3a and DNMT3b remained unaffected. HDAC inhibitor sodium butyrate and DNMT inhibitor Aza‐2′deoxycytidine recovered scopolamine‐impaired hippocampal‐dependent memory consolidation with concomitant increase in the expression of synaptic plasticity genes Brain‐derived neurotrophic factor (BDNF) and Arc and level of histone H3K9 and H3K14 acetylation and decrease in DNA methylation level. Sodium butyrate showed more pronounced effect than Aza‐2′deoxycytidine and their co‐administration did not exhibit synergistic effect on gene expression. Taken together, we showed for the first time that scopolamine‐induced up‐regulation of chromatin‐modifying enzymes, HDAC2 and DNMT1, leads to gene expression changes and consequent decline in memory consolidation. Our findings on the action of scopolamine as an epigenetic modulator can pave a path for ideal therapeutic targets.

     

Recent advances in small molecule drug delivery

The majority of new drugs, and new drug products, being developed and marketed by the pharmaceutical industry are small molecules. Oral administration remains the most common route of delivering such drugs, typically in the form of immediate-release tablets or capsules. While the immediate-release dosage forms dominate the market today, more specialized and rationalized products incorporating the concepts of drug delivery are being developed to overcome the physicochemical, physiological and pharmacological challenges inherent with the drugs, and to improve the treatment regimens for the patients. Today, these specialized concepts are increasingly being applied to first-generation products and not just products intended for the life cycle management of the franchise.     

Physiological and biochemical changes by nitric oxide and brassinosteroid in tomato (<Emphasis Type="Italic">Lycopersicon esculentum</Emphasis> Mill.) under drought stress

Drought stress produces many physiological and biochemical changes in plant affecting its life cycle and production. Oxidative damage and antioxidant defense responses are two components of plant to survive under drought stress. Nitric oxide (sodium nitroprusside, SNP) and brassinosteroid (24-epibrassinolide, EBL) were used in this experiment as single and combined application as foliar spray to study the mitigating effect of drought stress in two tomato genotypes EC-625652 (drought susceptible) and EC-620419 (drought tolerant). Drought stress produced harmful effect on number of leaves plant^?1, RWCL, fruit set percent, days to first fruit set, number of cluster plant^?1, lycopene content, fruit diameter and fruit yield. Plant produces reactive oxygen species (ROS), such as H₂O₂ in response to drought stress. Exogenous application of SNP and EBL, both in single and combined application, mitigated the deleterious effects of drought and improved drought tolerance by increasing SOD activity, fruit yield, and other physiological processes.     

Insights into the Role of Gasotransmitters Mediating Salt Stress Responses in Plants

Salinity stress is one of the most significant global issues that negatively affect plant growth and development. Modern agricultural practices have expanded the destructive effects of salinity stress, affecting plants through immediate osmotic stress, followed by a slow onset of ionic or hyper-osmotic stress. Plants alteration and resistance to salinity stress involve complex physiological, biochemical, and molecular systems to maintain homeostasis. As of late, the investigation of gaseous molecules in plants has attained much consideration, particularly for abiotic stress. Abiotic stresses generally initiate gasotransmitter (GT) generation in plants. In the interim, these GTs enhance the accumulation and activities of few antioxidant molecules, check the destructiveness of reactive oxygen species (ROS), and improve plant resilience under different stress conditions. The current review presented the role of gaseous molecules in plants under salinity stress, which include nitric oxide (·NO), hydrogen sulfide (H₂S), hydrogen gas (H₂), carbon monoxide (CO), methane (CH₄), and the only gaseous phytohormone ethylene. Further, we highlighted the underlying molecular mechanisms of the gasotransmitter signaling and cross-talks in salinity stress. Also, we presented a general update on the inclusion of GT in salt stress response, including the research gaps and its applications in the advancement of salinity-resistant plants.