It is well known that solid hypoxic tumour cells oxidise glucose through glycolysis, and the end product of this pathway is fermented into lactate which accumulates in the tumour microenvironment (TME). Initially, it was proclaimed that cancer cells cannot use lactate; therefore, they dump it into the TME and subsequently augment the acidity of the tumour milieu. Furthermore, the TME acts as a lactate sink with stope variable amount of lactate in different pathophysiological condition. Regardless of the amount of lactate pumped out within TME, it disappears immediately which still remains an unresolved puzzle. Recent findings have paved pathway in exploring the main role of lactate acidosis in TME. Cancer cells utilise lactate in the de novo fatty acid synthesis pathway to initiate angiogenesis and invasiveness, and lactate also plays a crucial role in the suppression of immunity. Furthermore, lactate re-programme the lipid biosynthetic pathway to develop a metabolic symbiosis in normoxic, moderately hypoxic and severely hypoxic cancer cells. For instance: severely hypoxic cancer cells enable to synthesizing poly unsaturated fatty acids (PUFA) in oxygen scarcity secretes excess of lactate in TME. Lactate from TME is taken up by the normoxic cancer cells whereas it is converted back to PUFAs after a sequence of reactions and then liberated in the TME to be utilized in the severely hypoxic cancer cells. Although much is known about the role of lactate in these biological processes, the exact molecular pathways that are involved remain unclear. This review attempts to understand the molecular pathways exploited by lactate to initiate angiogenesis, invasiveness, suppression of immunity and cause re-programming of lipid synthesis. This review will help the researchers to develop proper understanding of lactate associated bimodal regulations of TME.

Aim. The present investigation was designed to evaluate antiarthritic potential of fractions of hydroalcoholic extract from leaves ofP. alba.Materials and Methods.Plumeria albaL. leaves were extracted with hydroalcohol (30 : 70) to obtain hydroalcoholic extract ofP. alba. This extract was further fractionated with solvents ethyl acetate and n-butanol to obtain EAPA and BPA, respectively. These fractions were tested against formaldehyde and Freund’s complete adjuvant (FCA) induced arthritis. Arthritis assessment, paw volume, body weight, motor incoordination, and nociceptive threshold were measured. On day 21, the animals were sacrificed and histopathology was done.Results. The 100 and 200 mg/kg doses of EAPA and BPA caused a significant (P≤0.05–0.01) reduction in paw swelling in both models. Erythrocyte sedimentation rate (ESR) and spleen weight decreased significantly (P<0.01) in arthritic rats treated with extracts. There was significant (P<0.05) improvement in thymus weight in EAPA treated rats whereas significant (P<0.01) improvement was also seen in haemoglobin level (Hb) in diclofenac treated group. Motor incoordination and nociceptive threshold were also significantly (P≤0.05–0.01) improved.Conclusion. The present study suggests thatPlumeria albaL. has protective activity against arthritis and supports the traditional use ofP. albafor rheumatism and other inflammatory diseases.

Traditional medicinal plants have wide-reaching utilisation in the treatment of diabetes especially in developing countries where medical resources are meagre. Traditionally used anti-diabetic plants act by numerous mechanisms, however, only a few of them act through activation of the glucokinase enzyme. Glucokinase is a key regulatory enzyme in glucose metabolism thereby controls glucose homeostasis and insulin secretion. The present review significantly analyses the knowledge about various plant-based glucokinase activators including numerous phytochemicals which modulate the activity and gene expression of glucokinase and would provide data support and perspective regarding future research in the discovery and development of different plant-derived glucokinase activators. Graphical Abstract

Background: Eutectics are basically multi-component crystalline solids closely related to solid solutions. However, the structural organization of eutectics has not been studied in as much detail as solid solutions, which are defined based on the arrangement of a major (solvent) and a minor (solute) component in the crystal lattice. Purpose: The goal of this study is basically improvement in aqueous solubility of poorly water soluble drug i.e curcumin via its eutectic formation by using salicylic acid as coformer. Material and Method: Here the eutectic mixture of curcumin and salicylic acid was prepared by solvent evaporation technique for improving the dissolution behaviour of curcumin. DSC and FT-IR spectroscopy were used as analytical techniques for characterization of eutectic mixture. Result: The DSC and FT-IR spectroscopy conformed the formation of eutectic mixture and In-Vitro dissolution studies revealed an improved dissolution behaviour for eutectic mixture (69.38 %) as compared to the pure curcumin (40.53%). Conclusion: The study conclude that binary systems improved the dissolution behaviour of poorly water soluble drugs without changing the physiochemical and pharmacological properties of concerned API.

Cocrystallization process is a well-known technique for altering the pharmaceutical properties of drugs without modifying their actual pharmacological actions. Availability of a number of potential coformers make this technique more useful for implementation in pharmaceutical research area on newer and older API’s having pharmaceutical issues like poor solubility, stability profiles etc. Aspirin is a long-known antipyretic and anti-inflammatory drug belonging to BCS Class II having poor aqueous solubility. This API undergoes hydrolysis at higher temperature and in humid environment with the resultant degradation products being salicylic acid and acetic acid. Cocrystalization technique could be useful for improving its stability profile as the physicochemical properties of drugs get modified by their cocrystallization with coformers having better thermal stability as well higher solubility profile than API’s. In this study, aspirin and benzoic acid have been cocrystallized in a fixed stochiometric ratio (1:2) for improving its stability issues. Differential Scanning Calorimetry (DSC), Infra-Red spectroscopy technique (FTIR) and X-ray Diffraction (XRD) technique were used for analysis of cocrystals. Dissolution study was performed which revealed an improved dissolution profile of cocrystals compared to pure drug aspirin. Accelerated stability study was performed as per ICH guidelines for 6 months and stability profile of drug and cocrystals were compared by using HPLC technique, which exhibited a better stability profile of cocrystals compared to pure drug.