Quinoline Derivatives as Promising Scaffolds for Antitubercular Activity: A Comprehensive Review.

BACKGROUND: Heterocyclic compounds and their derivatives play a significant role in the design and development of novel quinoline drugs. Among the various pharmacologically active heterocyclic compounds, quinolines stand out as the most significant rings due to their broad pharmacological roles, specifically antitubercular activity, and their presence in plant-based compounds. Quinoline is also known as benzpyridine, benzopyridine, and 1-azanaphthalene. It has a benzene ring fused with a pyridine ring, and both rings share two carbon atoms. The importance of quinoline lies in its incorporation as a key component in various natural compounds found in medicinal plant families like Fumariaceae, Berberidaceae, Rutaceae, Papavaraceae, and others. OBJECTIVE: This article is expected to have a significant impact on the advancement of effective antitubercular drugs. Through harnessing the potent activity of quinoline derivatives, the research aims to make valuable contributions to combating tuberculosis more efficiently and ultimately reducing the global burden of this infectious disease. METHODS: Numerous nitrogen-containing heterocyclic compounds exhibit significant potential as antitubercular agents. These chemicals have fused aromatic nitrogen-heterocyclic nuclei that can change the number of electrons they have, which can change their chemical, physical, and biological properties. This versatility comes from their ability to bind with the receptors in multiple modes, a critical aspect of drug pharmacological screening. Among these compounds, quinoline stands out as it incorporates a stable fusion of a benzene ring with a pyridine nucleus. Quinolines have demonstrated a diverse range of pharmacological activities, including but not limited to anti-tubercular, anti-tumor, anticoagulant, anti-inflammatory, antioxidant, antiviral, antimalarial, anti-HIV, and antimicrobial effects. RESULTS: Some molecules, such as lone-paired nitrogen species, include pyrrole, pyrazole, and quinoline. These molecules contain nitrogen and take part in metabolic reactions with other molecules inside the cell. However, an excessive accumulation of reactive nitrogen species can lead to cytotoxicity, resulting in damage to essential biological macromolecules. Among these compounds, quinoline stands out as the oldest and most effective one, exhibiting a wide range of significant properties such as antitubercular, antimicrobial, anti-inflammatory, antioxidant, analgesic, and anticonvulsant activities. Notably, naturally occurring quinoline compounds, such as quinine, have proven to be potent antimalarial drugs. CONCLUSION: This review highlights quinoline derivatives' antitubercular potential, emphasizing recent research advancements. Utilizing IC50 values, the study emphasizes the efficacy of various quinoline substitutions, hybrids, and electron-withdrawing groups against MTB H37Rv. Continued research is essential for developing potent, low-toxicity quinoline derivatives to combat tuberculosis.

Mycotoxin detection in selected medicinal plants using chromatographic techniques.

Mycotoxins are toxic mycological products that when consumed, absorbed or inhaled cause sickness or even the death of humans. Therefore, the present study aimed to evaluate the contamination levels of mycotoxins (aflatoxins, AFB1 , AFB2 , AFG1 , AFG2 , and ochratoxin A, OTA) in selected medicinal herbs and shrubs using thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). A total of 15 samples of medicinal herbs and shrubs were selected. Among them, four samples were aflatoxin contaminated while two samples were ochratoxin A contaminated. The highest level of aflatoxin was detected in Justicia adhathoda (4,704.94 ppb) through HPLC (153.4 ppb) and through TLC, while the lowest level of aflatoxin was detected in Pegnum harmala (205.1 ppb) through HPLC. Similarly, the highest level of OTA was detected in Dodonia viscosa (0.53 ppb) through HPLC (0.5 ppb) and through TLC, while the lowest level was detected in J. adhathoda (O.11 ppb) through HPLC (0.4 ppb) and through TLC. The OTA concentration was very low, being negligible and below permissible limits. The present study concludes that there is a potential risk for the consumption of herbal decoctions. Therefore, regular monitoring and proper management of mycotoxins, including aflatoxins and OTA, in herbal medicines are needed to ensure the safety of herbal drugs to protect consumers.

Cytotoxicity of Moringa oleifera fruits on human liver cancer and molecular docking analysis of bioactive constituents against caspase-3 enzyme.

Moringa oleifera is an excellent source of phenolics and flavonoids comprise various pharmacological activities. The fourth widespread leading cause of the patients' death is liver cancer. This study was formulated to perform the antiproliferative activity of Moringa oleifera fruit (MOF) extract on human liver cancer HepG2 cells and computational validation of cell death. HepG2 cell line was treated with 25, 50, 75, 100, and 200 µg/ml of MOF extract for 48 hr, and antiproliferative activity was analyzed using MTT assay, nuclear condensation, annexin V-FITC/PI double stain, ROS generation, and apoptosis executioner enzyme caspase-3. MOF extract reduced the cell viability significantly (p Ë‚ .05) by increasing cellular apoptosis which was confirmed by annexin V-FITC/PI staining assay. In addition, MOF stimulated intracellular ROS production and subsequently induced caspase-3 activity depending upon dose. In silico analysis revealed the good binding interaction between amino acid residues of caspase-3 (PDB ID: 1GFW) protein and selected active constituents of MOF. PASS analyses of the phytoconstituents showed no violation of Lipinski's rule of five. Analysis of drug-likeness and toxicity measurement exhibited drug-like candidates with no predicted toxicity. In conclusion, this study showed the potential anticancer activity of MOF extract which may be valuable source for anticancer drug development. PRACTICAL APPLICATIONS: Moringa oleifera fruit extract induced the anti-proliferative activity against human hepatocellular carcinoma HepG2 cells through ROS-mediated apoptosis and activation of caspase-3 enzyme. Structure-based virtual screening study between bioactive components of Moringa oleifera fruits and apoptosis executioner caspase-3 enzyme has validated the anti-proliferative activity of Moringa oleifera fruit extract. Interestingly, active phytoconstituents of Moringa oleifera fruit exhibited drug-like candidates with no predicted toxicity. Thus, Moringa oleifera fruit could be used as valuable source for anticancer drug development against human liver cancer with relatively non-toxic to healthy cells.

Effects of temperature and storage on the antioxidant potential, polyphenols and Vitamin-C contents of azadirachta indica leave aqueous extract.

The aim of the study was to investigate the effects of effects of storage and temperature on the antioxidant potential, vitamin-C contents, total as well as selected individual phenolic acids and flavonoids of fresh aqueous leaves extract of Azadirachta Indica. The antioxidant activity of Azadirachta Indica leaves aqueous extract was determined by scavenging of DPPH free radical, while the phenolic compounds and vitamin-C contents by HPLC method. The analyses were carried out on crude extract of fresh leaves and after storage time of 1, 2 and 3 month at temperature of 20, 30 and 50°C. Storage for longer duration and rise in temperature caused decreasing the phenolic acids and vitamin C contents as well as antioxidant potential. Vitamin C contents were decreased up to 91% upon storage for 3 months at 50°C, while the anti-oxidant potential was decreased 29 %. The effect of storage time and temperature on individual phenolic acid and flavonoids were also remarkable, except ferulic acid which increased upon storage and rise in temperature.

Evaluation of hepatoprotective potential of Erythrina indica leaves against antitubercular drugs induced hepatotoxicity in experimental rats.

BACKGROUND: Erythrina indica Lam. traditionally used in the treatment of laxative, diuretic, worm infestation, liver ailment and joints pain. OBJECTIVE: To evaluate the antihepatotoxic potential of Erythrina indica against isoniazid (INH) and rifampicin (RIF) induced hepatotoxicity in rats. METHODS AND MATERIAL: Liver toxicity was induced by antitubercular drugs (INH+ RIF) at dose level of 50 mg/kg each, p.o for 28 days. 50% methanolic extract of Erythrina indica (100 and 200 mg/kg) were administered orally once daily for 28 days. The hepatoprotective activity was assessed using various biochemical parameters SGOT, SGPT, ALP, bilirubin, total protein, albumin and LDH. Meanwhile, in vivo antioxidant activities as SOD, CAT, GSH and, LPO were measured in liver homogenate also histological examinations were carried out to assess hepatoprotective activity. STATISTICAL ANALYSIS USED: The values were subjected to one way analysis of variance (ANOVA) followed by Tukey multiple compare test. Results were considered statistically significant when P < 0.05. RESULTS: Obtained results demonstrated that the treatment with Erythrina indica (E. indica) significantly prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, Erythrina indica significantly reduced the lipid peroxidation (P < 0.01 tp P < 0.001) in the liver tissue and restored activities of defense antioxidant enzymes GSH (2.15 ± 0.08 to 2.48 ± 0.99; P < 0.05), SOD (2.69 ± 0.752 to 3.712 ± 0.056; P < 0.05 to P < 0.01) and CAT (10.20 ± 0.58 to 12.59 ± 0.42; P < 0.05 to P < 0.001) towards normal. Histopathology of liver tissue showed that Erythrina indica attenuated the hepatocellular necrosis, regeneration and repair of cells toward normal. CONCLUSION: The results of this study strongly indicate the protective effect of Erythrina indica against liver injury which may be attributed to its hepatoprotective activity, and there by scientifically support its traditional use.

Ethanolic extract of Nigella sativa protects Fe(II) induced lipid peroxidation in rat's brain, kidney and liver homogenates.

The study describes the effect of ethanolic extract of Nigella sativa against Fe(II) induced lipid peroxidation. Basal and Fe(II) induced thiobarbituric acid reactive species (TBARS) production was significantly inhibited by the ethanolic extract of Nigella sativa at 25-200 µg/ml. Our data revealed that the extract has high DPPH radical scavenging activity at highest tested concentrations. The extract significantly chelated Fe(II) and scavenged hydroxyl (OH) radical at 25-200µg/ml concentration. The nutritional analysis was performed and carbohydrate, fats, fiber, protein, moisture and ash content were measured in the studied extract. The phytochemical analysis confirmed the presence of alkaloid, carbohydrate & sugar, glycosides, phenolic compounds, flavonoids, protein and amino acid, phytosterols, tannins, gum and mucilage. The extract also showed significant antimicrobial activities against 10 bacterial strains i.e. Salmonella typhi, Bacillus subtilis, Bacillus cereus, Klebsiella pneumonia, Escheria coli, Xanthomonas, Salmonella heidelberg, Staphylococcus aureus, Clostridium and Escheria coli (human) and 5 fungal strains i.e. Aspergillus niger, Entomola, Aspergillus flavus, Alternaria alternata and Penicillium. This study confirms the potential antioxidant and antimicrobial activities of ethanolic extract of Nigella sativa which can be considered not only as a diet supplement but can be used against a variety of free radical induced damage diseases.

Seasonal Affective Disorder (SAD): Role of Lamotrigine Augmentation to Anti-Depressant Medication in Winter Depression.

BACKGROUND: Many therapeutic options have been evaluated and tried for seasonal affective disorder (SAD) including bright light therapy (BLT), anti-depressants, beta-blockers and psychotherapy, but the data supporting use of mood-stabilizing agents is just handful in spite of this condition being understood most frequently to be associated with bipolar affective disorder II (BPAD II). So we planned to study role of Lamotrigine (Mood stabilizing agent) in SAD. MATERIALS AND METHODS: 30 patients of SAD who were prescribed lamotrigine in addition to antidepressant medications for a minimum of 8 weeks and were assessed for severity using HAM-D were selected retrospectively from the hospital records for this study. HAM-D scores at 2, 4 and 8 weeks were compared to baseline scores. STATISTICS ANALYSIS: Single tailed t-test was used to study the difference of means to assess the therapeutic response and pre/post analysis of change. Statistical significance was set at P < 0.05. RESULTS: Though no significant difference was seen in HAM-D Scores at 2 weeks of treatment compared to baseline, but results were statistically significant at 4 and 8 weeks of treatment with lamotrigine augmentation of antidepressant medications. CONCLUSION: We conclude that lamotrigine augmentation was found to be effective treatment strategy for managing winter depression phase of Seasonal Affective Disorder.

Effect of methanolic extract of Asparagus racemosus Willd. on lipopolysaccharide induced-oxidative stress in rats.

Lipopolysaccharide (LPS) induced oxidative stress and impairment of normal physiological function generally categorized by increased anxiety and reduced mobility. Therefore, the present study was to find out the effect Methanolic extract of Asparagus racemosus (MEAR ) in lipopolysaccharide (LPS)-induced oxidative stress in rats . LPS-induced oxidative stress in rats was measured by locomotor activity by photoactometer test, anxiety with elevated plus maze test and also studied the oxidative stress markers, nitric oxide and cytokines. The obtained data shows that LPS markedly exhausted (p<0.001) brain- reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) significantly increased (p<0.001) the level of malondialdehyde (MDA), nitric oxide and the activity of cytokines in the brain. MEAR supplementation resulted in normalization of brain GSH and CAT and SOD and decreases in the levels of MDA with reduction of nitric oxide and cytokines in the brain. The action of the extract at dose of 200 mg/kg was almost similar to the standard drug, quercetin (100mg/kg, p.o.). These present study conclude that MEAR administration significantly (P<0.05) reduced LPS- induced oxidative-stress and intensely suggest that Asparagus racemosus Willd. is a functionally newer type of cerebroprotective agent.

Evaluation of mycotoxins, mycobiota, and toxigenic fungi in selected medicinal plants of Khyber Pakhtunkhwa, Pakistan.

Medicinal plants are used worldwide to treat a variety of ailments. Due to the provenance of medicinal plants, they are subjected to contamination by moulds, which may be responsible for spoilage and production of mycotoxins. The investigation was designed to throw light on mycological and mycotoxicological status of some medicinal plants from Pakistan and the result showed 30 % and 26.7 % samples were contaminated with aflatoxins and ochratoxin A, respectively. Mould contamination was present in 90 % samples, of which 70 % exceeded the permissible limits. Opium poppy, licorice root, and Indian rennet were most contaminated samples. The predominant moulds found were Aspergillus flavus, Aspergillus niger, Aspergillus parasiticus, and Penicillium spp. and 31 % of the 47 isolates tested were found to be toxigenic. The findings indicate that the contamination in the medicinal plants may contribute to adverse human health problems. This information would prove helpful for regulatory agencies to establish limits for these contaminants in medicinal plants and will explore ways for export of herbal products to countries where more stringent permissible limits of mycotoxins exist. The study is first of its kind in the country reporting natural occurrence of mycotoxins in medicinal plants in Pakistan.

Development of HPLC method by UV-VIS detection for the quantification of phenolic acids in different Ocimum sanctum Linn. extracts.

A simple and rapid chromatographic method has been developed for the simultaneous determination of five phenolic acids including Gallic acid, Chloroganic acid, Syringic acid, Benzoic acid and Vanillic acid by HPLC with UV-VIS detector. These Phenolic acids were separated by analytical column Intersil ODS-3 C18, a gradient elution system of ACN and acidified water solution with 1ml/min flow rate and quantified in a total run of 30 minutes at 210nm wavelength. In the quantitative analysis of these compounds showed good regression (0.995-0.999). The limit of detection [LOD] and limit of quantification [LOQ] of these compounds were in the range of 0.15-0.46 and 0.42-2.47 ßg/mL. The average recoveries were between 95.8-103.1% and their RSD values were less than 3.34%. By the proposed method Gallic acid, Chloroganic acid and Syringic acid were found and quantified in Methanolic, Ethanolic and Acetonic extract of Ocimum sanctum Linn. leaves. While the two other phenolic acids benzoic acid and vanillic acid was not found in the extracts of Ocimum sanctum Linn. leaves.

Protective effects of Picrorhiza kurroa on cyclophosphamide-induced immunosuppression in mice.

OBJECTIVE: To study the immunomodulatory effect of ethanolic and aqueous extract of the rhizomes of Picrorrhiza kurroa (Scrophulariaceae) in normal and immunosuppressed mice models. MATERIALS AND METHODS: The rhizomes extract of Picrorrhiza kurroa was administered orally according to their body weight in mice. The study was carried out by various hematological and serological tests. The assessment of immunomodulatory activity on specific and non-specific immunity was studied by administration of test extract. The method of cyclophasphamide-induced immunosuppression was employed with slight modification to study the immunomodulatory potential of the extract. Plant extracts were administered by oral feeding canula to the test groups (groups III-VI), group I (control animals) and group II (model control animals) received same volume of normal saline (0.2 ml). Humoral antibody response to SRBC measurement of antibody titer by hemagglutination reaction was done. The mice belonging to the all groups were antigenically challenged with SRBC (0.5×10(9) cells/ml/100 g) on 10(th) day intraparitoneally. Cellular immune response (Foot pad reaction test) the edema was induced by injecting SRBC (0.025×10(9) cells) in left paw, and 0.025 ml of saline was injected in right paw. RESULTS: The plant extract showed protective effects on humoral immunity. The change in percentage deduction in footpad volume was also found significant (P<0.001). Administration of extract remarkably ameliorated both cellular and humoral antibody response. CONCLUSION: It is concluded that the test extracts possessed promising immunostimulant properties. But, the alcoholic extract is more potent than aqueous extract in producing delayed type hypersensitivity response.

Evaluation of antihepatotoxic potential of Solanum xanthocarpum fruit extract against antitubercular drugs induced hepatopathy in experimental rodents.

OBJECTIVE: To assess the hepatoprotective effect of Solanum xanthocarpum (S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals. METHODS: Ethanolic (50%) fruit extract of S. xanthocarpum (100, 200 and 400 mg/kg bw) was administered daily for 35 days in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs [isoniazid (I) 7.5 mg/kg, rifampicin (R) 10 mg/kg and pyrazinamide (P) 35 mg/kg] given orally as suspension for 35 days in rats. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatise (ALP), total bilirubin (TBL), albumin (ALB), total protein (TP), lactate dehydroginase (LDH), and serum cholesterol (CHL). Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were measured in rat liver homogenate. The biochemical observations were supplemented by histopathological examination. RESULTS: The results demonstrated that treatment with S. xanthocarpum significantly (P<0.05-P<0.001) and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, S. xanthocarpum significantly (up to P<0.001) reduced the LPO in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels. Histopathology of the liver tissue showed that S. xanthocarpum attenuated the hepatocellular necrosis and led to reduction in inflammatory cells infiltration. CONCLUSIONS: The results of this study strongly indicate the protective effect of S. xanthocarpum against liver injury which may be attributed to its hepatoprotective activity, and thereby scientifically support its traditional use.

Oral lipid based drug delivery system (LBDDS): formulation, characterization and application: a review.

The major problem in oral drug formulations is low and erratic bioavailability, which mainly results from poor aqueous solubility. This may lead to high inter- and intra subject variability, lack of dose proportionality and therapeutic failure. The improvement of bio-availability of drugs with such properties presents one of the greatest challenges in drug formulations. Oral lipid based formulations are attracting considerable attention due to their capacity to increase the solubility, facilitating gastrointestinal absorption and reduce or eliminate the effect of food on the absorption of poorly water soluble, lipophilic drug and thus increasing the bioavailability. The present review outlines the recent findings on self-emulsifying drug delivery system (SEDDS), self-micro/nanoemulsifying drug delivery system (SMEDDS/SNEDDS) and evaluation of these formulations published over the past decade. The application of lipid based formulations as a promising system for the oral delivery of many therapeutic agents including traditional medicine (TM) has also been examined in the current review.