Sesquiterpene lactones (STLs) make a diverse and huge group of bio-active constituents that have been isolated from several plant families. However, the greatest numbers are present in Asteraceae family having more than 3000 different reported structures. Recently several researchers have reported that STLs have significant antioxidant and anticancer potentials. To investigate the antioxidant, anticancer and antinociceptive potentials of STLs, gravity column chromatography technique was used for isolation from the biologically rich chloroform fraction of Artemisia macrocephala Jacquem. The antioxidant activity of the isolated STLs was determined by DPPH and ABTS free radical scavenging activity, anticancer activity was determined on 3 T3, HeLa and MCF-7 cells by MTT assay while the antinociceptive activity was determined through acetic acid induced writhings, tail immersion method and formalin induced nociception method. The results showed that the STLs of Artemisia macrocephala possesses promising antioxidant activity and also it decreased the viability of 3 T3, HeLa and MCF-7 cells and mild to moderate antinociceptive activity. Sesquiterpenes lactones (STLs) are widely present in numerous genera of the family Asteraceae (compositae). They are described as the active constituents used in traditional medicine for the treatment of various diseases. The present study reveals the significant potentials of STL and may be used as an alternative for the management of cancer. Anyhow, the isolated compound is having no prominent antinociceptive potentials.

Tissue damage is associated with pain, which is an alarming sign. Aspirin and morphine have been widely used in recent decades for management of pain. Medicinal herbs have been in use for treatment of different diseases for centuries. Many of these herbs possess analgesic activity with relatively less incidences of adverse effects. The strong positive correlation of alkaloids in medicinal plants for analgesic activity persuades an intention to determine possible analgesic activity of total alkaloids extracted from the selected medicinal plants using animal models to answer its possible mechanisms. Crude alkaloids from selected medicinal plants (Woodfordia fruticosa, Adhatoda vasica, Chenopodium ambrosioides, Vitex negundo, Peganum harmala and Broussonetia papyrifera) were extracted as per reported literature. The test crude alkaloids were screened foracute toxicity study. Writhings induced by acetic acid, tail immersion method and formalin-induced nociception assay procedures were used for possible analgesic effects of the crude alkaloids. Crude alkaloids were safe up to dose of 1250 mg/kg body weight in mice. The alkaloids significantly reduced the abdominal constrictions, and increased the time for paw licking response in both phases with a significant raise in latency time in nociception models (P ≤ 0.05). Moreover, the antinociceptive response was significantly attenuated by pretreatment with naloxone suggesting involvement of the opioid receptors for possible antinociceptive action. Crude alkaloids of Woodfordia fruticosa and Peganum harmala showed prominent analgesic potentials through inhibition of peripheral as well as central nervous system mechanisms. Further work is required for isolation of the pharmacologically active constituents.

Schiff bases are a class of organic compounds with azomethine moiety, exhibiting a wide range of biological potentials. In this research, six chiral Schiff bases, three ‘S’ series (H1–H3) and three ‘R’ series (H4–H6), were synthesized. The reaction was neat, which means without a solvent, and occurred at room temperature with a high product yield. The synthesized compounds were evaluated for analgesic potential in vivo at doses of 12.5 and 25 mg/kg using acetic-acid-induced writhing assay, formalin test, tail immersion and hot plate models, followed by investigating the possible involvement of opioid receptors. The compounds H2 and H3 significantly (*** p < 0.001) reduced the writhing frequency, and H3 and H5 significantly (*** p < 0.001) reduced pain in both phases of the formalin test. The compounds H2 and H5 significantly (*** p < 0.001) increased latency at 90 min in tail immersion, while H2 significantly (*** p < 0.001) increased latency at 90 min in the hot plate test. The ‘S’ series Schiff bases, H1–H3, were found more potent than the ‘R’ series compounds, H4–H6. The possible involvement of opioid receptors was also surveyed utilizing naloxone in tail immersion and hot plate models, investigating the involvement of opioid receptors. The synthesized compounds could be used as alternative analgesic agents subjected to further evaluation in other animal models to confirm the observed biological potential.

Amnesia is a major health problem prevalent in almost every part of the world specifically in old age peoples. Vanillin analogues have played an important role in the field medicines. Some of them have been documented to be promising inhibitors of cholinesterases and could therefore, be used as antidepressant, anti-Alzheimer and as neuroprotective drugs. In this connection, the present study was designed to synthesize new vanillin analogues (SB-1 to SB-6) of varied biological potentials. The synthesized compounds were investigated as inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes and as scavengers of DPPH and ABTS free radicals followed by behavioural antiamnesic evaluation in mice. The compounds; SB-1, SB-3, SB-4 and SB-6 more potently inhibited AChE with IC₅₀ values of 0.078, 0.157, 0.108, and 0.014 μM respectively. The BChE was more potently inhibited by SB-3 with IC₅₀ of 0.057 μM. Moreover, all of the tested compounds exhibited strong antioxidant potentials with promising results of SB-3 against DPPH with IC₅₀ of 0.305 μM, while SB-5 was most active against ABTS with IC₅₀ of 0.190 μM. The in-vivo studies revealed the improvement in memory deficit caused by scopolamine. Y-Maze and new object recognition test showed a considerable decline in cognitive dysfunctions. In Y-Maze test the spontaneous alteration of 69.44 ± 1% and 84.88 ± 1.35% for SB-1 and 68.92 ± 1% and 80.89 ± 1% for SB-3 at both test doses were recorded while during the novel object recognition test the Discrimination Index percentage of SB-1 was more pronounced as compared to standard drug. All compounds were found to be potent inhibitors of AChE, BChE, DPPH, and ABTS in vitro however, SB-1 and SB-3 were comparatively more potent. SB-1 was also more active in reclamation of memory deficit caused by scopolamine. SB-1 and SB-3 may be considered as excellent drug candidates for treating amnesia subjected to toxicological evaluations in other animal models.

In this study, Chenopodium murale Linn. extracts have been evaluated for its in vitro antioxidant, enzyme inhibition, and in vivo neuropharmacological properties in streptozotocin (STZ)-induced memory impairment in rat model. First, the plant was subjected to extraction and fractionation, then quantitative phytochemical analysis was performed to estimate the major phytochemical groups in the extract where high amounts of phenolics and saponins were detected in crude and chloroform extract. The highest total phenolic contents, total flavonoid contents, and total tannin content were also recorded in crude extract and chloroform fraction. The in vitro antioxidant potential of chloroform fraction was high with IC₅₀ value of 41.78 and 67.33 μg/mL against DPPH and ABTS radicals, respectively, followed by ethyl acetate fraction. The chloroform fraction (ChMu-Chf) also exhibited potent activity against glucosidase with IC₅₀ of 89.72 ± 0.88 μg/mL followed by ethyl acetate extract (ChMu-Et; IC₅₀ of 140.20 ± 0.98 μg/mL). ChMu-Chf again exhibited potent activity against acetylcholinesterase (AChE) with IC₅₀ of 68.91 ± 0.87 μg/mL followed by ChMu-Et with IC₅₀ of 78.57 ± 0.95 μg/mL. In vivo memory impairment was assessed using the novel object discrimination task, Y-maze, and passive avoidance task. Ex vivo antioxidant enzyme activities and oxidative stress markers like catalase, superoxide dismutase (SOD), malondialdehyde, and glutathione were quantified, and the AChE activity was also determined in the rat brain. No significant differences were observed amongst all the groups treated with crude, chloroform, and ethyl acetate in comparison with positive control donepezil group in connection to initial latency; whereas, the STZ diabetic group displayed a significant fall in recall and retention capability. The blood glucose level was more potently lowered by chloroform extract. The crude extract also increased the SOD level significantly in the brain of the treated rat by 8.01 ± 0.51 and 8.19 ± 0.39 units/mg at 100 and 200 mg/kg body weight (P < 0.01, n = 6), whereas the chloroform extract increased the SOD level to 9.41 ± 0.40 and 9.72 ± 0.51 units/mg, respectively, at 75 and 150 mg/kg body weight as compared to STZ group. The acetylcholine level was also elevated to greater extent by chloroform fraction that might contain a potential inhibitor of acetylcholinesterase. Treatment with C. murale ameliorated cognitive dysfunction in behavioral study, and provided significant defense from neuronal oxidative stress in the brain of the STZ-induced diabetic rats. Thus C. murale Linn. could be an inspiring plant resource that needs to be further investigated for isolation of potential compounds in pure form and their evaluation as a potent neuropharmacological drug.

Depression is a serious psychological disorder which negatively affects human feelings and actions. The use of antidepressants is the therapy of choice while treating depression. However, such drugs are associated with severe side effects. There is a need for efficient and harmless drugs. In this connection, the present study was designed to synthesize several substituted benzodiazepine derivatives and explore their antidepressant potentials in an animal model. The chalcone backbone was initially synthesized, which was then converted into several substituted benzodiazepine derivatives designated as 1–6. The synthesized compounds were identified using spectroscopic techniques. The experimental animals (mice) after acclimatation were subjected to forced swim test (FST) and tail suspension test (TST) after oral administration of the synthesized compounds to evaluate their antidepressant potentials. At the completion of the mentioned test, the animals were sacrificed to determine GABA level in their brain hippocampus. The chloro-substituent compound (2) significantly reduced the immobility time (80.81 ± 1.14 s; p < 0.001 at 1.25 mg/kg body weight and 75.68 ± 3.73 s with p < 0.001 at 2.5 mg/kg body weight dose), whereas nitro-substituent compound (5) reduced the immobility time to 118.95 ± 1.31 and 106.69 ± 3.62 s (p < 0.001), respectively, at the tested doses (FST). For control groups, the recorded immobility time recorded was 177.24 ± 1.82 s. The standard drug diazepam significantly reduced immobility time to 70.13 ± 4.12 s while imipramine reduced it to 65.45 ± 2.81 s (p < 0.001). Similarly, in the TST, the compound 2 reduced immobility time to 74.93 ± 1.14 s (p < 0.001) and 70.38 ± 1.43 s (p < 0.001), while compound 5 reduced it to 88.23 ± 1.89 s (p < 0.001) and 91.31 ± 1.73 s (p < 0.001) at the tested doses, respectively, as compared to the control group immobility time (166.13 ± 2.18 s). The compounds 1, 3, 4, and 6 showed weak antidepressant responses as compared to compounds 2 and 5. The compounds 2 and 5 also significantly enhanced the GABA level in the brain’s hippocampus of experimental animals, indicating the possible involvement of GABAergic mechanism in alleviating the depression which is evident from the significant increase in mRNA levels for the α subunit of the GABA_A receptors in the prefrontal cortex of mice as well. From the results, it can be concluded that compound 2 and 5 could be used as alternative drugs of depression. However, further exploration in this connection is needed in other animal models in order to confirm the observed results in this study.