Tacrine is a drug used in the treatment of Alzheimer’s disease as a cognitive enhancer and inhibitor of the enzyme acetylcholinesterase (AChE). However, its clinical application has been restricted due to its poor therapeutic efficacy and high prevalence of detrimental effects. An attempt was made to understand the molecular mechanisms that underlie tacrine and its analogues influence over neurotherapeutic activity by focusing on modulation of neurogenesis, neuroinflammation, endoplasmic reticulum stress, apoptosis, and regulatory role in gene and protein expression, energy metabolism, Ca2+ homeostasis modulation, and osmotic regulation. Regardless of this, analogues of tacrine are considered as a model inhibitor of cholinesterase in the therapy of Alzheimer’s disease. The variety both in structural make‐up and biological functions of these substances is the main appeal for researchers’ interest in them. A new paradigm for treating neurological diseases is presented in this review, which includes treatment strategies for Alzheimer’s disease, as well as other neurological disorders like Parkinson’s disease and the synthesis and biological properties of newly identified versatile tacrine analogues and hybrids. We have also shown that these analogues may have therapeutic promise in the treatment of neurological diseases in a variety of experimental systems.
A spinal cord injury (SCI) occurs when the spinal cord is deteriorated or traumatized, leading to motor and sensory functions lost even totally or partially. An imbalance within the generation of reactive oxygen species and antioxidant defense levels results in oxidative stress (OS) and neuroinflammation. After SCI, OS and occurring pathways of inflammations are significant strenuous drivers of cross‐linked dysregulated pathways. It emphasizes the significance of multitarget therapy in combating SCI consequences. Polyphenols, which are secondary metabolites originating from plants, have the promise to be used as alternative therapeutic agents to treat SCI. Secondary metabolites have activity on neuroinflammatory, neuronal OS, and extrinsic axonal dysregulated pathways during the early stages of SCI. Experimental and clinical investigations have noted the possible importance of phenolic compounds as important phytochemicals in moderating upstream dysregulated OS/inflammatory signaling mediators and axonal regeneration’s extrinsic pathways after the SCI probable significance of phenolic compounds as important phytochemicals in mediating upstream dysregulated OS/inflammatory signaling mediators. Furthermore, combining polyphenols could be a way to lessen the effects of SCI.
Alzheimer’s disease (AD) is a devastating neurodegenerative disease that mostly affects the elderly population. Mechanisms underlying AD pathogenesis are yet to be fully revealed, but there are several hypotheses regarding AD. Even though free radicals and inflammation are likely to be linked with AD pathogenesis, still amyloid-beta (Aβ) cascade is the dominant hypothesis. According to the Aβ hypothesis, a progressive buildup of extracellular and intracellular Aβ aggregates has a significant contribution to the AD-linked neurodegeneration process. Since Aβ plays an important role in the etiology of AD, therefore Aβ-linked pathways are mainly targeted in order to develop potential AD therapies. Accumulation of Aβ plaques in the brains of AD individuals is an important hallmark of AD. These plaques are mainly composed of Aβ (a peptide of 39–42 amino acids) aggregates produced via the proteolytic cleavage of the amyloid precursor protein. Numerous studies have demonstrated that various polyphenols (PPHs), including cyanidins, anthocyanins, curcumin, catechins and their gallate esters were found to markedly suppress Aβ aggregation and prevent the formation of Aβ oligomers and toxicity, which is further suggesting that these PPHs might be regarded as effective therapeutic agents for the AD treatment. This review summarizes the roles of Aβ in AD pathogenesis, the Aβ aggregation pathway, types of PPHs, and distribution of PPHs in dietary sources. Furthermore, we have predominantly focused on the potential of food-derived PPHs as putative anti-amyloid drugs.
Exploring the metabolic potency of fungi as camptothecin producers raises the hope of their usage as an industrial source of camptothecin, due to their short-life span and the feasibility of metabolic engineering. However, the tiny yield and loss of camptothecin productivity of fungi during storage and sub-culturing are challenges that counteract this approach. Marine fungi could be a novel source for camptothecin production, with higher yield and reliable metabolic sustainability. The marine fungal isolate Penicillium chrysogenum EFBL # OL597937.1 derived from the sponge “Cliona sp.” has been morphologically identified and molecularly confirmed, based on the Internal Transcribed Spacer sequence, exhibiting the highest yield of camptothecin (110 μg/L). The molecular structure and chemical identity of P. chrysogenum derived camptothecin has been resolved by HPLC, FTIR and LC-MS/MS analyses, giving the same spectroscopic profiles and mass fragmentation patterns as authentic camptothecin. The extracted camptothecin displayed a strong anti-proliferative activity towards HEP-2 and HCT-116 (IC50 values 0.33–0.35 µM). The yield of camptothecin was maximized by nutritional optimization of P. chrysogenum with a Plackett-Burman design, and the productivity of camptothecin increased by 1.8 fold (200 µg/L), compared to control fungal cultures. Upon storage at 4 °C as slope culture for 8 months, the productivity of camptothecin for P. chrysogenum was reduced by 40% compared to the initial culture. Visual fading of the mycelial pigmentation of P. chrysogenum was observed during fungal storage, matched with loss of camptothecin productivity. Methylene chloride extracts of Cliona sp. had the potency to completely restore the camptothecin productivity of P. chrysogenum, ensuring the partial dependence of the expression of the camptothecin biosynthetic machinery of P. chrysogenum on the chemical signals derived from the sponge, or the associated microbial flora. This is the first report describing the feasibility of P. chrysogenum, endozoic of Cliona sp., for camptothecin production, along with reliable metabolic biosynthetic stability, which could be a new platform for scaling-up camptothecin production.