Utilization of xylose enriched extract from spent lemongrass hydrolysate for clavulanic acid production using Streptomyces clavuligerus (MTCC 1142).

The main goal of this study was to provide possible alternative production medium containing xylose enriched spent lemongrass hydrolysate with glycerol as a feedstock and corn gluten meal as a nitrogen source for their ability to support the cell growth of the Streptomyces clavuligerus MTCC 1142 for the production of clavulanic acid. The xylose was extracted from spent lemongrass by using 0.25% dilute nitric acid and further partial purification of acid spent hydrolysate was performed using ion exchange resin. The method was optimized using xylose enriched hydrolysate as feed stock combined with glycerol at ratio 1:1 and growing the selected strain aerobically in media at neutral pH containing 5 mM phosphate ion concentration and using corn gluten meal as a nitrogen source, fermenting at a temperature of 28-30 °C for 96 h and 0.59 g/L clavulanic acid was effectively produced. These results demonstrate the feasibility of using spent lemongrass as feedstock for the cultivation of S. clavuligerus to produce clavulanic acid.

Andrographis paniculata mitigates first-line anti-tubercular drugs-induced nephrotoxicity in Wistar rats.

CONTEXT: Anti-tubercular drugs (ATDs) mediated adverse drug reactions are major concerns for clinicians to treat tuberculosis infection. This study aimed to investigate Andrographis paniculata extract-based phytotherapy to combat the nephrotoxic effects caused by ATDs therapy. METHODS: Reno-protective effect of A. paniculata extract in ATDs-induced rats was evaluated through LPO, GSH, CAT, SOD, GST, urea, creatinine, uric acid, and histopathological studies. Standardization of the extract was performed using RP-HPLC and FTIR analysis. Whereas, the effect of A. paniculata extract on ATDs induced genetic perturbation was analyzed using micronucleus assay. Moreover, the expression level of the xenometabolic gene was investigated using RT-PCR to explore the therapeutic mechanism. RESULTS: The nephrotoxic effect of ATDs was indicated by elevated levels of LPO and renal function markers along with the reduced activity of renal antioxidants. An up-regulated expression profile of NAT gene and histological alterations were observed in renal tissue however, micronucleated PCEs were observed in bone marrow cells. Concomitant treatment with A. paniculata extract revealed a noticeable amelioration of elevated oxidative stress markers, gene expression levels, genotoxic perturbation, and histological alterations in a dose-dependent manner. CONCLUSION: Hence, the present study using A. paniculata leaf extract confirmed to play effective phytotherapy against ATDs induced renal toxicity.

Ameliorative potential of Adhatoda vasica against anti-tubercular drugs induced hepatic impairments in female Wistar rats in relation to oxidative stress and xeno-metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Adhatoda vasica Nees is widely used herb of indigenous system to treat various ailments especially upper respiratory tract infections. Not only, anti-tubercular efficacy of crude extract and phytoconstituents of A. vasica has been documented but its hepatoprotective role against various drugs mediated hepatic alterations in different animal models has also been observed. BACKGROUND AND PURPOSE: Isoniazid, rifampicin and pyrazinamide (H-R-Z) are anti-tubercular drugs normally prescribed by health professionals for the treatment of tuberculosis, however along with their medical effectiveness these drugs also exhibit hepatotoxicity among TB patients. Unexpectedly, substantial toxicological data on the metabolism of anti-TB drugs are available but the mystery behind these xenobiotics is too complex and partly implicit. In this study, we further explored the hepatotoxic effects of these xeno-metabolic products and their amelioration by Adhatoda vasica Nees by elucidating its mechanistic action. METHODS: We generated a hepatotoxic rodent model by oral administration of H, R and Z (30.85, 61.7 and 132.65 mg/kg body weight) drugs for 25 days in Wistar rats. Additionally, to achieve hepatoprotection two different doses of Adhatoda vasica Nees ethanolic leaf extract (200 and 300 mg/kg body weight) were used along with H-R-Z dosage, orally and once daily for 25 days and tried to ascertain their mechanistic action. For this, initially phytoconstituents of the extract were evaluated followed by extract standardization using RP-HPLC and FTIR methods. Furthermore, antioxidant activity of the extract was analyzed by DPPH assay. Finally, different treated groups were analyzed for hepatic oxidative stress markers, antioxidant markers, histopathological changes and gene expression study including CYP2E1, CYP7A1, NAT, NR1I2 and UGT1A1 genes involved in phase I and phase II xeno-metabolism. RESULTS: Estimated content of vasicine in RP-HPLC method and free-radical scavenging activity in DPPH assay was found to be 134.519 ± 0.00269µg/10mg of leaf extract and 47.81 µg/mL respectively. In H-R-Z treated group, a significant increase in the levels of thiobarbituric acid, significant reduction in the levels of GSH, and enzymatic markers and marked changes in hepatic histological architecture were observed. In addition, there was significance up-regulation of CYP7A and NAT genes, down-regulation of CYP2E1 gene and insignificant expression levels of NR1I2 and UGT1A1 genes were observed in H-R-Z group. Conversely, high dose of A. vasica extract effectively diminished these alterations by declining oxidative stress and boosting of antioxidant levels. In addition, it acted as bi-functional inducer of both phase I (CYP2E1) and phase II (NAT and UGT1A1) enzyme systems. CONCLUSION: Hence, we concluded that anti-TB drugs exposure has potential to generate reactive metabolites that eventually cause hepatotoxicity by altering oxidant-antioxidant levels and their own metabolism. This study not only emphasized on xeno-metabolism mediated hepatic alterations but also explore the benefit of A. vasica on these toxic insults.

Tannic Acid-Stabilized Self-Degrading Temperature-Sensitive Poly(2-n-propyl-2-oxazoline)/Gellan Gum Capsules for Lipase Delivery.

In recent years, stable hydrogen-bonded stimuli-responsive polymer capsules have been receiving great interest for the encapsulation and release of sensitive molecules such as lipase enzymes. Compartmental capsules having a liquid gel core stabilized with temperature-responsive hydrogen-bonded multilayers are advantageous over other conventional systems because of their ability to maintain hydrophilic lipase and other hydrophobic compounds in compatible protected molecular vehicle environments and prolong their native properties, e.g., in the body. In this work, we report a methodology to stabilize an aqueous liquid gellan gum (GG) core in a capsule using neutral and nontoxic building blocks, namely, poly(2-n-propyl-2-oxazoline) (PnPrOx) and tannic acid (TA), to fabricate temperature-responsive capsules, comprising both lipase and hydrophobic oil droplets. The capsules were fabricated by adding GG droplets to a PnPrOx suspension at a temperature (T) higher than its cloud point temperature (TCP). Notably, the formed capsules were not stable in water without TA stabilization via hydrogen bonding. Scanning electron microscopy (SEM) investigations of the GG/building block interphase revealed that the collapsed PnPrOx globules that are present above the TCP stabilized the GG interphase as a Pickering emulsion, while undergoing a configurational transformation into its linear form by interacting with TA in the next step of capsule formation resulting in a smooth PnPrOx/TA capsule wall. The encapsulation efficiencies of the capsules for model fluorescent molecules were found to be 52, 54, and 24% for FITC-dextran, rhodamine, and Nile red, respectively. The stability experiments exhibited swelling and shell thinning at certain locations followed by complete rupture of the capsules at 37 °C, while the capsules were stable for several weeks at temperatures below the TCP of PnPrOx. The capsules were found to be stable in stimulated gastric fluid (SGF) for several hours at 37 °C while successfully releasing the encapsulated lipase and Nile red (model hydrophobic compound) in stimulated intestinal fluid (SIF). The released lipase was found to retain almost 100% of its activity. The reported capsules have high potential for use as carriers for encapsulation and release of a variety of payloads ranging from proteins and vitamin supplements to enzymes and probiotics through the oral route of administration.

Two-dimensional cancer theranostic nanomaterials: Synthesis, surface functionalization and applications in photothermal therapy.

In recent years, novel two-dimensional (2D) nanomaterials are of great interest for diverse potential applications such as device fabrication, energy storage, sensing and theranostics because of their superlative physical features namely, large surface area, minimal thickness, tunable composition and easier surface modification methods. Rapid exploration in design and fabrication of 2D nano-structures have opened new avenue for cancer theranostics as it can encapsulate group of cancer cells and inflict major damage with great specificity in a non-invasive manner. Among the reported 2D materials such as graphene and its derivatives, metallic compounds, transition metal dichalcogenides (TMDC), black phosphorous and MXenes (e.g., carbides, nitrides, or carbonitrides), 2D nanomaterials based on graphene and TMDCs have gathered most of the limelight in this field due to their easily tunable properties. In this review, we summarize recent progress in the design of 2D theranostic nanomaterials, functionalization methods and their applications in photothermal therapy (PTT) as well as synergistic cancer therapy. We have also addressed the different modes of cellular entry of 2D nanomaterials into tumor cells based on their unique structural properties and investigated different methodologies to enhance PTT effect by optimizing the physico-chemical properties of the 2D sheets. Recent progress on in vitro and in vivo short and long term biocompatibility, immunotoxicity and excretion of the decorated structure is also highlighted. Investigation of the interaction of 2D nanomaterial with hematological factors such as RBC and WBC is of paramount importance as they are key indicators in in vivo responses, and this investigation will give a better solution for overcoming direct inflammation and infection related issues of the animal system. Besides, investigations on addressing the ways to incorporate polymer linkers and drug conjugates on to the surface of 2D materials, multiplexing capability, and the influence of surface functionalization on PTT effect is vital for future developments in clinical level diagnosis and cancer therapy. Finally, we conclude our opinion on current challenges and future prospective on meeting the various demands of advanced cancer imaging and therapies.