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.

Berberis aristata Ameliorates Testicular Toxicity Induced by Combination of First-Line Tuberculosis Drugs (Rifampicin + Isoniazid + Pyrazinamide) in Normal Wistar Rats.

First-line antituberculosis drugs, namely, isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA), contribute to diverse pathological complications. Testicular toxicity is one such complication. Berberis aristata DC is an herb with potentially curative characteristics. The aim of this study was to test whether extract of Berberis aristata DC (Berberidaceae) has curing potential against testicular toxicity. Characterization of extract was done using ultra-performance liquid chromatography along with acute toxicity testing. Antioxidant activity of extract was checked by DPPH inhibition assay and H2O2 scavenging assay. Rats were dosed once daily for 28 days in groups: control group (saline), toxicant group (30.85 mg/kg body weight INH + 61.7 mg/kg body weight RIF + 132.65 mg/kg body weight PZA), treatment groups (TB drugs + 150/300 mg/kg body weight extract) and standard group (TB drugs +100 mg/kg body weight silymarin). Spectrophotometric evaluations of lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione-S-transferase (GST), and catalase (CAT) content in testes were done using standard protocols. DNA fragmentation and histopathological studies were performed to check the damage at the cellular level. Acute toxicity studies revealed LD50 > 5 g/Kg body weight of B. aristata extract. IC50 for DPPH free-radical scavenging activity and H2O2 scavenging assay were 44.78 µg/mL and 85.28 µg/mL, respectively. Results revealed significant increase in thiobarbituric acid reactive substances, decrease in glutathione and different antioxidants levels, DNA fragmentation pattern, and changes in histology in toxicant group. All the changes were absent in high-dose (300 mg/kg body weight) extract treatment group. This work proved that B. aristata extract has protective efficacy against testicular damage caused by anti-TB drugs.

Preserving neural retina through re-emerging herbal interventions.

Eye related diseases such as glaucoma, diabetic retinopathy, cataract, conjunctivitis are very common worldwide. With the current scenario India will be among the top five countries in the number of glaucoma cases. Limited discovery of successful drugs for the treatment of such diseases led scientists to look towards the use of conventional sources for treatment. Herbal extracts from Ayurveda have remained an important part of treatment regime in many parts of world even today. For this reason, local herbs possessing curative properties are still being used by local inhabitants due to its anti-inflammatory and antioxidant properties. Because retinal damage involves alterations in oxidative enzymes, blood flow changes and increase in apoptotic signals, herbal extracts are being tested for their ability to moderate antioxidant machinery and trigger neuroprotective pathways. The present review summarizes some of such herbal extracts which have been tested for their neuroprotective role in eye related diseases. The active components that exert neuroprotective effects have also been discussed along with possible mechanisms of action.