Advancement in the contemporary clinical diagnosis and treatment strategies of insomnia disorder.

This review is intended to provide an updated summary of, but not limited to, classification, etiopathogenesis, diagnosis, and treatment strategies for insomnia disorder. The severity of insomnia symptoms irrespective of co-existing primary medical condition/s in the studied patients classified insomnia as 'insomnia disorder' to prioritize the clinical attention on insomnia (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition). The frequency and duration of symptoms further divided insomnia into chronic, short-term, and other insomnia disorder (International Classification of Sleep Disorders, Third Edition). This disorder is a phenomenal state of hyperarousal developed and perpetuated by environmental, behavioral, cognitive, genetic, socioeconomic, preexisting medical factors. Overarching physiological, cortical, behavioral, and cognition changes in hyperarousal manifest insomnia disorder. It, sometimes, leads to the co-occurrence of other chronic medical condition/s. The contemporary diagnosis of insomnia disorder needs to consider modified diagnostic criteria, growing evidence on insomnia disorder symptoms, associated factors, co-existing medical condition/s (if any) to identify the subjective severity of insomnia disorder and design a treatment plan. The recommended treatment strategies include cognitive-behavioral therapy for insomnia (CBTI) and pharmacotherapy. However, CBTI lacks accessibility, qualified facilitators, and pharmacotherapy has limitations like side effects, physiological tolerance/dependence. The investigation of phytocompounds subdued these drawbacks of existing treatments as some compounds showed anti-insomniac potential. Furthermore, complementary alternative medicines (CAMs) like mindfulness-based practices, acupuncture, listening to music, Yogasanas, Pranayama, digital cognitive behavioral therapy for insomnia (dCBTI) during bedtime proved supportive in insomnia disorder treatment.

Ethnomedical, phytochemical and pharmacological insights on an Indian medicinal plant: The balloon vine (Cardiospermum halicacabum Linn.).

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiospermum halicacabum Linn. (C. halicacabum) is one of the well-known leafy green vegetables in India. It is an herbaceous climber from the Sapindaceae family which is found in almost every Continent and Oceania. In the traditional Indian medicine systems, this plant is used for the treatment of rheumatism, abdominal pain, orchitis, dropsy, lumbago, skin diseases, cough, nervous disorders, and hyperthermia. AIM OF THE REVIEW: This review presents the current information about ethnomedical uses and progress on geographical distribution, pharmacological activities, phytochemistry, micropropagation, and toxicity of C. halicacabum. Also, critically summarizes the relationship between the reported pharmacological activities and the traditional usages along with the future perspectives for research on this medicinal plant. MATERIALS AND METHODS: The data on C. halicacabum were collected using multiple internet sources such as Google Scholar, Science Direct, Taylor & Francis, PubMed, Web of Science, Springer Link, Wiley online, and plant databases. RESULTS: Chemical characterization using LC-MS/MS, HPLC, and NMR exposed the presence of chlorogenic acid, caffeic acid, coumaric acid, luteolin-7-o-glucuronide, apigenin-7-o-glucuronide, and chrysoeriol in different parts of C. halicacabum. Based on the outcomes of this review, the main bioactive compounds found in C. halicacabum include phenols, phenolic acids, flavonoids, flavonoid glycosides, and flavonoid glucuronides. Besides the above-mentioned constituents, palmitic acid, oleic acid, stearic acid, linolenic acid, eicosenoic acid, and arachidic acid are the compounds that constitute the fatty acid profile of C. halicacabum seeds. Specifically, Cardiospermin, a bioactive compound isolated from the root extract of C. halicacabum has been recognized for its anxiolytic activity. Moreover, C. halicacabum showed a broad spectrum of pharmacological activities including anti-inflammatory, anti-arthritic, anti-diabetic, anxiolytic activity, antiulcer, apoptotic activity, antibacterial, antiviral, anti-diarrheal, antioxidant, hepatoprotective, and nephroprotective properties. However, the bioactive compounds responsible for most of the above therapeutic properties have not been elucidated till now. CONCLUSION: Phytochemicals from C. halicacabum showed noticeable pharmacological effects against plethora of health disorders. Some of the traditional applications were supported by modern scientific studies, however, more pharmacological evaluations should be conducted to validate other traditional uses of C. halicacabum. Despite C. halicacabum's vast pharmacological activity, additional human clinical trials are needed to determine the potent and safe dosages for the treatment of various health abnormalities. Besides, bioassay-guided isolation of active constituents, pharmacokinetic evaluations and identification of their mode of action are recommended for future investigations on C. halicacabum to unveil its therapeutic drug leads. Overall, this review suggests that C. halicacabum could be a new source of functional foods.

Brassica juncea (L.) Czern. leaves alleviate adjuvant-induced rheumatoid arthritis in rats via modulating the finest disease targets - IL2RA, IL18 and VEGFA.

Brassica juncea (BJ) is a familiar edible crop, which has been used as a dietary ingredient and to prepare anti-inflammatory/anti-arthritic formulations in Ayurveda. But, the scientific validation or confirmation of its therapeutic properties is very limited. This study was performed to determine the efficiency of BJ leaves for the treatment of Rheumatoid arthritis using in vivo and in silico systems. Standard in vitro procedures was followed to study the total phenolic, flavonoid contents and free radical scavenging ability of the extracts of BJ. The effective extract was screened and the presence of bioactive chemicals was studied using HPLC. Further, the possible therapeutic actions of the BJ active principles against the disease targets were studied using PPI networking and docking analysis. IL2RA, IL18 and VEGFA are found to be the potential RA target and the compounds detected from BJ extract have shown great binding efficiency towards the target from molecular docking study. The resulting complexes were then subject to 100 ns molecular dynamics simulation studies with the GROMACS package to analyze the stability of docked protein-ligand complexes and to assess the fluctuation and conformational changes during protein-ligand interactions. To confirm the anti-arthritic activity of BJ, the extract was tested in CFA-induced arthritic Wistar rats. The test groups administered with BJ extract showed retrieval of altered hematological parameters and substantial recovery from inflammation and degeneration of rat hind paw.Communicated by Ramaswamy H. Sarma.

Food obesogens as emerging metabolic disruptors; A toxicological insight.

Human food is composed of loads of chemicals derived naturally as well as unintentionally through environmental sources. Food additives added purposefully, play an important role in the palatability of foods. Most additives are synthetic whose essentiality in food processing is well-known however their health risks are not overlooked. The palatability of food should not only stimulate our eating desire alone but, also assure sufficient quality and safety. Application of food additives varies from region to region due to cultural or ethnic differences and the local food availability. There are about more than ten thousand chemicals allowed in food whereas due to weak enforcement, it becomes onerous for regulatory bodies identifying chemicals that are inadequately or not tested at all for safety. The hiking population and urbanization in many industrialized and developing countries resulted in life-style changes including culinary and eating choices. Particularly, the modern way of this globalised life demands ready-to-cook or ready-made foods, snacks, sweets, soft drinks, desserts, confectionery and so on. These sorts of food would be most uninteresting unless processed with additives. This puts food industries under demand to robustly supply foods that are either partially, fully or ultra-processed using plenty of additives. Recent research warns consuming food additives may result in serious health risks, not only for children but also for adults. Growing body of studies on food additives in various experimental animals, cell cultures, and human population suggest elevation of number of obesity and diabetes risk factors i.e. adiposity, dyslipidemia, weight gain, hyperglycaemia, insulin resistance, glucose intolerance, energy imbalance, hormonal intervention etc. Hence, it is important to identify and explore food obesogens or obesogenic food additives posing potential impact. Based on the recent toxicological findings, the review aspires to establish the association between exposure of food obesogen and metabolic disruption which may help filling knowledge gaps and distributing more knowledge, awareness and effective measures to implement treatment and preventive strategies for metabolic syndrome.

Fortification of raw rice and rice flour using Cissus quadrangularis L. (veldt grape) stem powder to overcome osteoporosis and its associated skeletal complication through staple diet.

This study aimed to prepare the fortified rice/flour with Cissus quadrangularis (CQ) stem powder to eliminate nutritional deficiency and improve bone health. Mineral analysis by atomic absorption spectroscopy revealed that the CQ stem has adequate quantities of calcium, magnesium, and a moderate amount of phosphorous to meet the Recommended Dietary Allowance (RDA). Thus, the rice and flour were fortified with freeze-dried CQ stem powder to improve its nutraceutical contents. The fortification was done using standard vacuum impregnation and blending process. Furthermore, the recuperative activity of prepared fortified rice (CQFR) and flour (CQFF) was tested in chemically induced osteoporosis and osteoarthritis animal models. The efficiency of CQ fortified diet against these complications was confirmed by hematology, radiology, and histopathological analysis. The rat groups fed with CQFF/CQFR diet showed significant improvement from calcium deficiency and its allied physiological damage. Thus, this study confirms that the CQ fortified rice would provide recovery from skeletal complications associated with calcium deficiency through fixing both homeostasis and bio-accessibility of the calcium. PRACTICAL APPLICATIONS: Micronutrient and mineral deficiency is relatively higher in the regions where rice/rice products are consumed as a staple diet. Dietary intake of calcium and some essential minerals have major influences on bone and joint health. Cissus quadrangularis (CQ) is a familiar herb, conventionally used in India to fix broken bones and strengthen the skeletal system. The Atomic absorption spectroscopy data from this study showed that the CQ stem holds a high amount of calcium and other essential minerals to promote skeletal health. Preparation of fortified rice and flour with CQ stem would be a beneficial source of the essential minerals/ bioactive principles to promote and sustain skeletal health in the underprivileged population. These study data substantiated the practical application of producing the CQ fortified nutraceutical staple diet, especially to the people who are afflicted with morbid skeletal complications.

Regulatory mechanisms of heme regulatory protein BACH1: a potential therapeutic target for cancer.

A limited number of overexpressed transcription factors are associated with cancer progression in many types of cancer. BTB and CNC homology 1 (BACH1) is the first mammalian heme-binding transcription factor that belongs to the basic region leucine zipper (bZIP) family and a member of CNC (cap 'n' collar). It forms heterodimers with the small musculoaponeurotic fibrosarcoma (MAF) proteins and stimulates or suppresses the expression of target genes under a very low intracellular heme concentration. It possesses a significant regulatory role in heme homeostasis, oxidative stress, cell cycle, apoptosis, angiogenesis, and cancer metastasis progression. This review discusses the current knowledge about how BACH1 regulates cancer metastasis in various types of cancer and other carcinogenic associated factors such as oxidative stress, cell cycle regulation, apoptosis, and angiogenesis. Overall, from the reported studies and outcomes, it could be realized that BACH1 is a potential pharmacological target for discovering new therapeutic anticancer drugs.

Evaluation of the anti-rheumatic properties of thymol using carbon dots as nanocarriers on FCA induced arthritic rats.

Rheumatoid Arthritis (RA) is an autoimmune disease that commences as inflammation and progressively destroys the articular joint. In this study, we assess the anti-rheumatic potential of the monoterpenoid class of thymol conjugated with Carbon Dots (CDs). Waste biomass in the form of dried rose petals was chosen as a precursor for the synthesis of CDs via a one-step hydrothermal bottom-up methodology. The prepared CDs exhibited absorption in the near-visible region, and unique excitation-dependent emission behaviour was confirmed from UV-Visible and fluorescence measurements. The surface morphology of CDs was confirmed by SEM and HR-TEM analysis to be quasi-spherical particles with an average size of ∼5-6 nm. The presence of various functional moieties (hydroxyl, carbonyl, and amino) was confirmed via FT-IR measurement. The graphitization of CDs was confirmed by the D and G bands for sp2 and sp3 hybridization, respectively, through Raman analysis. Esterification methodology was adopted to prepare the CDs-thymol conjugate and confirmed via FT-IR analysis. CDs play the role of a nanocarrier for thymol, an anti-arthritic agent. The bioactive compound of thymol showed potent anti-arthritic activity against RA targets through in silico docking studies. Further, the in vivo studies revealed that CDs-thymol conjugates (10 mg per kg body weight) showed a significant reduction in rat paw volume along with reduced levels of RF and CRP (2.23 ± 0.42 IU ml-1 and 16.96 ± 0.22 mg ml-1) when compared to the disease control rats. X-ray radiography and ultrasonic imaging revealed less bone destruction, joint derangement, and swelling in arthritis-induced Wistar rats. They could also potentially improve the Hb (14.14 ± 0.19), RBC (6.01 ± 0.11), PCV (6.01 ± 0.11) levels and elevate the status of antioxidant enzymes (GPx, SOD, MDA), and the activity was comparable to the standard drug, ibuprofen (10 mg kg-1), suggesting that the CDs-thymol conjugate at 10 mg kg-1 could act as a strong anti-arthritic agent. This work is evidence for the utilization of waste biomass as a value-added product such as a nanocarrier for biomedical applications.

Attenuation of protein glycation by functional polyphenolics of dragon fruit (Hylocereus polyrhizus); an in vitro and in silico evaluation.

Chronic hyperglycemia and oxidative stress promote non-enzymatic glycation that leads to the production of advanced glycation end products (AGEs). AGEs casue significant damage to physiological proteins which result in several complications. The scenario also corresponds to the chronic consumption of a diet rich in AGEs. Despite understanding these mechanisms at the molecular level, the discovery of new drugs for these complications is under progress. Natural compounds might have great therapeutic potential for treating glycative consequences. In view of this, the study aimed to evaluate fruit extracts of Hylocereus polyrhizus towards determining its phenolics and flavonoid contents, as well as assessing it's in vitro antiglycative potential through the use of multistage glycation markers (early, intermediate and end stage products of ß-aggregation) in sugar-protein model. In vitro hypoglycemic activity of H. polyrhizus extracts was evaluated through α-amylase and α glucosidase inhibitory activities. In vitro antioxidant potential of the fruit extracts was also examined against different free radical types including DPPH and ABTS. Among the different in vitro assays performed, methanolic and acetone extracts of the fruit, with higher phenolics and flavonoid content, have exerted significant antiglycation and antioxidant activities than other extracts namely aqueous, ethanol, hydro-ethanol, hydro-methanol, and petroleum ether. Ultra-Performance Liquid Chromatography coupled with Electrospray Ionization Mass Spectrometry (UPLC-ESI-MS/MS) analysis was employed to identify active polyphenolics that may be responsible for the antiglycative potential of H. polyrhizus. The analysis revealed some high-profile compounds that have well documented for their therapeutic benefits. Additionally, In silico analysis also showed the possible connection between identified compounds and mechanisms of action. 4- Prenylresveratrol, Vicenin, and Luteolin had observed as effectively interact with target protein in molecular docking analysis. This suggests H. polyrhizus as a good source of anti-glycation and antioxidants that may have potential applications for the treatment and prevention of glycation associated diabetic and aging complications.

Momordica cymbalaria improves reproductive parameters in alloxan-induced male diabetic rats.

Male reproductive dysfunction is one of the common complications of diabetes mellitus that causes infertility. This study was designed to investigate the protective effect of Momordica cymbalaria (M. cymbalaria) extracts on diabetes mediated reproductive toxicity in male Wistar rats. The induction of diabetes was performed using a single intraperitoneal injection of alloxan (120 mg/kg). Skin and seed extracts (250 and 500 mg/kg) of M. cymbalaria were orally administered to alloxan-induced diabetic male rats for 28 days. Postprandial blood glucose (PBG) levels were recorded at 7-day interval for four weeks. The effects of the treatment on blood glucose, weight of reproductive organs, sperm count, testosterone levels, antioxidant capacity, and histomorphology were evaluated. Treatment with the above extracts of M. cymbalaria significantly (p < 0.05) improved the reproductive parameters as well as the antioxidant levels superoxide dismutase (SOD) and glutathione-s-transferase (GST) in the diabetic rats. Also, oral treatment with M. cymbalaria extracts significantly reduced the PBG and malondialdehyde (MDA) levels. Further, it revived the histomorphology of reproductive organs in diabetic rats. Interestingly, skin extract at a dose of 500 mg/kg was found to be more efficient in elevating the level of testosterone and sperm count in the diabetic rats. Based on the results, it is clear that M. cymbalaria not only regulates the postprandial blood glucose levels but also improves the reproductive health in the diabetic state.

Evaluation of anti rheumatic activity of Piper betle L. (Betelvine) extract using in silico, in vitro and in vivo approaches.

Rheumatoid Arthritis is a chronic, inflammatory, and systemic autoimmune disease, it affects elders worldwide. Herbal medicines have been used for the treatment of various ailments from ancient times. Betelvine (Piper betle L.) leaves have long been used in Asian countries as a medicine to relieve pain and some metabolic diseases. The present study of methanolic extract of phytochemical analysis confirms the presence of alkaloids, tannins, terpenoids, saponins, steroids, total flavonoids and total phenols. GC-MS analysis of MeOH extract of Piper betle (PBME) revealed the presence of 40 bioactive compounds. In vitro antioxidant and anti-inflammatory assays showed greater inhibitory effect. The anti-arthritic effects of PBME at 250 and 500 mg/kg concentration showed recovery from joint damage in in vivo rat model. Among the 40 GC-MS derived bioactives, 4-Allyl-1,2-Diacetoxybenzene exhibited the higher interactions with minimized binding energy to the RA targets of MMP 1 (-6.4 kcal/mol), TGF-ß (-6.9 kcal/mol), IL-1ß (-5.9 kcal/mol). Further, the effect of PBME extract against RA molecular disease targets (IL-1ß, MMP1 and TGF- ß) were studied using Real-time PCR. These results substantiate that P. betle leaves could be a source of therapeutics for the treatment of rheumatoid arthritis.

Cissus quadrangularis (veldt grape) attenuates disease progression and anatomical changes in mono sodium iodoacetate (MIA)-induced knee osteoarthritis in the rat model.

The Cissus quadrangularis (CQ) stem has interesting nutritional and pharmacological properties to promote the health of the skeletal system. It is a well-recognized plant in the conventional system of medicine in India for treating bone and joint-associated complications. This study focuses on identifying the active constituents from the stem and root extracts of CQ and validating its anti-osteoarthritic activity by the in vivo model. Notable levels of phenolics and flavonoids were found in the ethanol extracts of both CQ stem (CQSE) and root (CQRE), among other solvent fractions. UPLC-MS/MS analysis of these selective extracts resulted in different classes of active compounds from both positive and negative ionization modes. By analyzing their mass spectra and fragmentation pattern, 25 active compounds were identified. The CQSE and CQRE extracts, along with the standard drug (naproxen), were further tested in mono-sodium iodoacetate-induced experimental OA animals. The modulatory effects of the test extracts were assessed by haematology, synovial and cartilage marker profiling, radiology and histopathological analysis. The in vivo findings from the biochemical and physiological studies have led to the conclusion that the CQSE extract is a good choice for the management of OA. The results were substantially better than CQ root extract and naproxen drug-treated groups. Thus, CQS has bioactive constituents, which could facilitate recovery from joint tissue damage, cellular metabolism and associated risk factors attributable to dysfunctions in OA incidence and progression.

Antidiabetic and hypolipidemic efficacy of skin and seed extracts of Momordica cymbalaria on alloxan induced diabetic model in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Momordica cymbalaria, a wild vegetable belongs to the Cucurbitaceae family, has long been used as a food and a remedy for diabetes mellitus in the Asian native medicinal system. AIM OF THE STUDY: This study aims to evaluate the efficacy of ethanolic extract of skin (EESK) and methanolic extract of seed (MESE) of M. cymbalaria (MC), for their hypoglycemic and hypolipidemic effects in alloxan induced diabetic rats. MATERIALS AND METHODS: The diabetes induced rats were given skin and seed extracts at doses 250 and 500 mg/kg b.w. p.o. for 28 days. Alloxan monohydrate (120 mg/kg) was used to induce diabetes mellitus. Daily food and water intake were assessed. Blood glucose levels and body weights were measured every 7 days throughout the experiment. Antioxidant assays, different biochemical and glycemic parameters were evaluated. Histopathological studies on pancreas, liver and kidney were also studied. RESULTS: Treatment of EESK and MESE showed dose significant decrease in fasting blood glucose level (FBG) in experimental diabetic animals with significant reduction in food and water intake and increase in body weight. Findings confirmed the hypoglycemic and hypolipidemic effects of EESK and MESE in the experimental groups. The impaired glucose tolerance and altered activities of the hepatic enzymes such as AST, ALT and ALP levels of diabetic rats were significantly improved by the administration of EESK and MESE. Oral treatment with MC extract for 28 days demonstrated significant protective effects on the lipid profile, biochemical parameters and antioxidant levels. Besides, biochemical findings were supported by histopathological investigations. CONCLUSION: These results suggest that the treatment with EESK and MESE of MC at a dose of 500 mg/kg b.w. have better protective effects against hyperglycemia, hyperlipidemia and oxidative stress generated during diabetes justifying the use of the plant in traditional systems of medicine.

Food advanced glycation end products as potential endocrine disruptors: An emerging threat to contemporary and future generation.

Mankind exposure to chemicals in the past century has increased dramatically throughout environment. There is no question that chemicals interfere with the physiology of biological system. Abundance of chemicals is documented to be detrimental to human and wildlife. The mammalian endocrine system is comprised of many interacting tissues mediate themselves through hormones that are essential for metabolism, growth and development. Humans secrete over fifty different hormones to orchestrate major physiological functions however; these vital functions can be intervened by huge number of internal and external chemical stressors that are identified as endocrine disruptors. Advanced glycation end products (AGEs), familiarly known as Maillard products, formed through non-enzymatic glycation whose production is augmented on aging as well as environmental stressors. Processed foods have become very popular today due to their taste, convenience, and inexpensiveness. Manufacture of these day-to-day foods involves extreme temperatures on processing results in the formation of AGEs could independently promote oxidative stress, aging, diabetes, cancer, degenerative diseases, more fascinatingly hormonal disruption is the subject of interest of this review. Based on some substantial observations documented till time, we discuss the emergence of dietary AGEs as potential endocrine disruptors by emphasizing their occurrence, mechanisms and participation in endocrine interruption. Both economically and in terms of human life, AGEs may represent an enormous cost for the future society. Therefore, by explicating their novel role in endocrine diseases, the review strives to make an impact on AGEs and their exposure among public as well as scientific communities.