Terpenoids as potential phytoconstituent in the treatment of diabetes: From preclinical to clinical advancement.

BACKGROUND: Diabetes mellitus, a hyperglycemic condition associated with multitudinous organ dysfunction, is a hallmark of the metabolic disorder. This life-threatening condition affects millions of individuals globally, harming them financially, physically and psychologically in the course of therapy. PURPOSES: The course therapy for illnesses has undergone ground-breaking transformations due to recent technical advances and insights. Alternatively, the administration of hyperglycemia-reducing agents results in several complications, including severe cardiovascular disease, kidney failure, hepatic problems, and several dermatological conditions. Consideration of alternate diabetic therapy having minimal side effects or no adverse reactions has been driven by such problems. STUDY DESIGN: An extensive literature study was conducted in authoritative scientific databases such as PubMed, Scopus, and Web of Science to identify the studies elucidating the bioactivities of terpenoids in diabetic conditions. METHODS: Keywords including 'terpenoids', 'monoterpenes', 'diterpenes', 'sesquiterpenes', 'diabetes', 'diabetes mellitus', 'clinical trials', 'preclinical studies', and 'increased blood glucose' were used to identify the relevant research articles. The exclusion criteria, such as English language, duplication, open access, abstract only, and studies not involving preclinical and clinical research, were set. Based on these criteria, 937 relevant articles were selected for further evaluation. RESULTS: Triterpenes can serve as therapeutic agents for diabetic retinopathy, peripheral neuropathy, and kidney dysfunction by inhibiting several pathways linked to hyperglycemia and its complications. Therefore, it is essential to draw special attention to these compounds' therapeutic effectiveness and provide scientific professionals with novel data. CONCLUSION: This study addressed recent progress in research focussing on mechanisms of terpenoid, its by-products, physiological actions, and therapeutic applications, particularly in diabetic and associated disorders.

In-depth Mechanism, Challenges, and Opportunities of Delivering Therapeutics in Brain Using Intranasal Route.

Central nervous system-related disorders have become a continuing threat to human life and the current statistic indicates an increasing trend of such disorders worldwide. The primary therapeutic challenge, despite the availability of therapies for these disorders, is to sustain the drug's effective concentration in the brain while limiting its accumulation in non-targeted areas. This is attributed to the presence of the blood-brain barrier and first-pass metabolism which limits the transportation of drugs to the brain irrespective of popular and conventional routes of drug administration. Therefore, there is a demand to practice alternative routes for predictable drug delivery using advanced drug delivery carriers to overcome the said obstacles. Recent research attracted attention to intranasal-to-brain drug delivery for promising targeting therapeutics in the brain. This review emphasizes the mechanisms to deliver therapeutics via different pathways for nose-to-brain drug delivery with recent advancements in delivery and formulation aspects. Concurrently, for the benefit of future studies, the difficulties in administering medications by intranasal pathway have also been highlighted.

Cannabis effectiveness on immunologic potency of pulmonary contagion.

Respiratory illnesses and its repercussions are becoming more prevalent worldwide. It is necessary to research both innovative treatment and preventative techniques. Millions of confirmed cases and fatalities from the COVID-19 epidemic occurred over the previous two years. According to the review research, cannabinoids are a class of medicines that should be considered for the treatment of respiratory conditions. Cannabinoids and inhibitors of endocannabinoid degradation have illustrated advantageous anti-inflammatory, asthma, pulmonary fibrosis, and pulmonary artery hypotension in numerous studies (in vitro and in vivo). It has been also noted that CB2 receptors on macrophages and T-helper cells may be particularly triggered to lower inflammation in COVID-19 patients. Since the majority of lung tissue contains cannabinoid receptors, cannabis can be an effective medical tool for treating COVID-19 as well as pulmonary infections. Notably, CB2 and CB1 receptors play a major role in immune system modulation and anti-inflammatory activities. In this review, we put forth the idea that cannabis might be helpful in treating pulmonary contagion brought on by viral integration, such as that caused by SARS-CoV-2, haemophilus influenza type b, Streptococcus pneumoniae, influenza virus, and respiratory syncytial virus. Also, a detailed overview of CB receptors, intricate mechanisms, is highlighted connecting link with COVID-19 viral structural modifications along with molecular basis of CB receptors in diminishing viral load in pulmonary disorders supported through evident literature studies. Further, futuristic evaluations on cannabis potency through novel formulation development focusing on in vivo/in vitro systems can produce promising results.

Potential molecular pathways of angiotensin receptor blockers in the brain toward cognitive improvement in dementia.

The alarming rise of cognitive impairment and memory decline and limited effective solutions present a worldwide concern for dementia patients. The multivariant role of the renin-angiotensin system (RAS) in the brain offers strong evidence of a role for angiotensin receptor blockers (ARBs) in the management of memory impairment by modifying glutamate excitotoxicity, downregulating inflammatory cytokines such as interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)α, inhibiting kynurenine aminotransferase (KAT)-II, nucleotide-binding domain, leucine-rich-containing family and pyrin-domain-containing-3 (NLRP3) inflammasomes, boosting cholinergic activity, activating peroxisome proliferator-activated receptor (PPAR)-γ, countering cyclooxygenase (COX) and mitigating the hypoxic condition. The present work focuses on the intricate molecular mechanisms involved in brain-RAS, highlighting the role of ARBs, connecting links between evidence-based unexplored pathways and investigating probable biomarkers involved in dementia through supported preclinical and clinical literature.

The SH-SY5Y cell line: a valuable tool for Parkinson's disease drug discovery.

INTRODUCTION: Owing to limited efficient treatment strategies for highly prevalent and distressing Parkinson's disease (PD), an impending need emerged for deciphering new modes and mechanisms for effective management. SH-SY5Y-based in vitro neuronal models have emerged as a new possibility for the elucidation of cellular and molecular processes in the pathogenesis of PD. SH-SY5Y cells are of human origin, adhered to catecholaminergic neuronal attributes, which consequences in imparting wide acceptance and significance to this model over conventional in vitro PD models for high-throughput screening of therapeutics. AREAS COVERED: Herein, the authors review the SH-SY5Y cell line and its value to PD research. The authors also provide the reader with their expert perspectives on how these developments can lead to the development of new impactful therapeutics. EXPERT OPINION: Encouraged by recent research on SH-SY5Y cell lines, it was envisaged that this in vitro model can serve as a primary model for assessing efficacy and toxicity of new therapeutics as well as for nanocarriers' capacity in delivering therapeutic agents across BBB. Considering the proximity with human neuronal environment as in pathogenic PD conditions, SH-SY5Y cell lines vindicated consistency and reproducibility in experimental results. Accordingly, exploitation of this standardized SH-SY5Y cell line can fast-track the drug discovery and development path for novel therapeutics.

Biomacromolecule-based nanocarrier strategies to deliver plant-derived bioactive components for cancer treatment: A recent review.

The quest for safe chemotherapy has attracted researchers to explore anticancer potential of herbal medicines. Owing to upsurging evidence of herbal drug's beneficial effects, hopes are restored for augmenting survival rates in cancer patients. However, phytoconstituents confronted severe limitations in terms of poor absorption, low-stability, and low bioavailability. Along with toxicity issues associated with phytoconstituents, quality control and limited regulatory guidance also hinder the prevalence of herbal medicines for cancer therapy. Attempts are underway to exploit nanocarriers to circumvent the limitations of existing and new herbal drugs, where biological macromolecules (e.g., chitosan, hyaluronic acid, etc.) are established highly effective in fabricating nanocarriers and cancer targeting. Among the discussed nanocarriers, liposomes and micelles possess properties to cargo hydro- and lipophilic herbal constituents with surface modification for targeted delivery. Majorly, PEG, transferrin and folate are utilized for surface modification to improve bioavailability, circulation time and targetability. The dendrimer and carbon nanotubes responded in high-loading efficiency of phytoconstituent; whereas, SLN and nanoemulsions are suited carriers for lipophilic extracts. This review emphasized unveiling the latent potential of herbal drugs along with discussing on extended benefits of nanocarriers-based delivery of phytoconstituents for safe cancer therapy owing to enhanced clinical and preclinical outcomes without compromising safety.

Anti-cancer potential of substituted "amino-alkyl-rhodamine" derivatives against MCF-7 human breast cancer cell line.

Breast cancer is the most prevalent diagnosed cancer among women and the main cause of morbidity and mortality. As for breast cancer, MCF-7 cells are an important candidate since they are widely utilized in research for estrogen receptor (ER)-positive breast cancer cell assays, and various sub-clones have been identified to reflect different classes of ER-positive tumors with varied levels of nuclear receptor expression. Rhodamines and its derivatives have shown a great interest over the past two decades due to their excellent structural and spectroscopic properties. Rhodamine derivatives have been widely investigated for their mitochondrial targeting and chemotherapeutic properties. Rhodamine derivatives, in particular, have been widely investigated for their therapeutic properties. In this regard, several studies have shown that rhodamine dye derivatives have promising in vitro and in vivo therapeutic efficacy. The present study deals with potential anticancer activity of few synthesized rhodamine derivatives against MCF-7 cell lines.

Pathogenesis of Huntington's Disease: An Emphasis on Molecular Pathways and Prevention by Natural Remedies.

BACKGROUND: Huntington's disease is an inherited autosomal dominant trait neuro-degenerative disorder caused by changes (mutations) of a gene called huntingtin (htt) that is located on the short arm (p) of chromosome 4, CAG expansion mutation. It is characterized by unusual movements, cognitive and psychiatric disorders. OBJECTIVE: This review was undertaken to apprehend biological pathways of Huntington's disease (HD) pathogenesis and its management by nature-derived products. Natural products can be lucrative for the management of HD as it shows protection against HD in pre-clinical trials. Advanced research is still required to assess the therapeutic effectiveness of the known organic products and their isolated compounds in HD experimental models. SUMMARY: Degeneration of neurons in Huntington's disease is distinguished by progressive loss of motor coordination and muscle function. This is due to the expansion of CAG trinucleotide in the first exon of the htt gene responsible for neuronal death and neuronal network degeneration in the brain. It is believed that the factors such as molecular genetics, oxidative stress, excitotoxicity, mitochondrial dysfunction, neuroglia dysfunction, protein aggregation, and altered UPS leads to HD. The defensive effect of the natural product provides therapeutic efficacy against HD. Recent reports on natural drugs have enlightened the protective role against HD via antioxidant, anti-inflammatory, antiapoptotic, and neurofunctional regulation.

Effect of Cliothosa aurivilli on Paclitaxel-induced Peripheral Neuropathy in Experimental Animals.

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious complication leading to painful episodes of parasthesia and numbness in hands and feet. The present drugs that have been used for symptomatic treatment yield inconclusive results in trials and assorted side effects. Thus, there is a pressing demand for development of therapeutically efficacious strategy to combat CIPN. The present study investigates about the effect of a marine sponge; Cliothosa aurivilli (CA) on paclitaxel (PT)-induced peripheral neuropathy in mice. Peripheral neuropathy was induced by intoxication with chemotherapeutic drug PT (2 mg/kg; i.p.) for 5 days consequently. Subsequent treatment with aqueous extract of CA (100 and 200 mg/kg) and standard drug methylcobalamin (MCA) (5 mg/kg) was done and results compared statistically. Neuropathic pain sensations were assessed using various behavioural and locomotory models and evaluated on 0th, 7th and 14th days. Kinovea software was used for video path-tracking of animals and total distance travelled calculated. The results indicated clear signs of improvement post 10 days of PT intoxication in CA-treated groups when compared PT challenged group. A significant reduction in pain behaviours in mechanical allodynia, cold chemical allodynia and thermal hyperalgesia models, improvement in sensory motor coordination, locomotor activity, and distance travelled in closed field model reveals that CA possesses potential ameliorating effect against PT-induced neuropathic pain symptoms. The extract notably improved the movement of the PT challenged animals which was shown by the video path-tracking software and total distance travelled by those animals.