Therapeutic potential of flavonoids in ovalbumin induced asthma in mice model.

OBJECTIVES: Desmodium triquetrum DC (Fabaceae) is a plant commonly used in Indian traditional medicine to treat allergies. Asthma is a severe condition, with an estimated 300 million deaths annually, which could increase to 400 million by 2025. Flavonoids, a class of compounds found in many plants, have been found to have beneficial effects in treating asthma. In this study, researchers focused on three flavonoids, Baicalein, Naringin, and Neohesperidin, derived from Desmodium triquetrum DC, to investigate their potential as a treatment for asthma. METHODS: The study used an aerosolized ovalbumin-induced asthma model to evaluate the effects of the flavonoids on various substances in bronchoalveolar lavage fluid, including total differential leukocyte, nitrite, nitrate, TNF, IL-4, and IL-13. The researchers also measured the levels of myeloperoxidase and malondialdehyde in the lungs. RESULTS: The results showed that ovalbumin-induced airway hyper-responsiveness led to a significant increase in pro-inflammatory cytokine levels. However, the flavonoids significantly decreased the severity of airway inflammation. Histopathology results also supported the effectiveness of the flavonoids. These findings suggest that these flavonoids could be a supplementary and alternative treatment for asthma by inhibiting the pro-inflammatory pathway. CONCLUSIONS: The findings suggest that the isolated compounds have the potential to act cumulatively to decrease the levels of the tested cytokines, normalize eosinophil and activated lymphocyte counts, and significantly reduce MPO and MDA. This indicates a possible respiratory mechanism of action for the drugs.

Effects of Yoga therapy in teaching oral hygiene practice and tooth brushing skills in patients with Parkinson's disease: A qualitative study.

BACKGROUND: Parkinson's disease is a chronic neurodegenerative disorder associated with heterogeneous symptoms. Though it is characterized by means of four distinct motor symptoms such as resting tremors, muscular rigidity, bradykinesia, and postural instability. These patients also have deficits in fine motor skills while performing simple tasks such as brushing their own teeth, taking bath, remembering small details, and writing skills. The study aimed to qualitatively evaluate the effectiveness of Yoga therapy in teaching oral hygiene practice and subsequently, on tooth brushing skills in patients who were diagnosed with Parkinson's disease. MATERIALS AND METHODS: This qualitative study was conducted on 100 patients diagnosed with Parkinson's disease. Institutional ethical committee permission was obtained prior to commencing the study. Written informed consent was obtained from patients or their caregivers before conducting this study. Detailed clinical history was recorded and gender characteristics were noted down. In the present study, there were 67 female and 33 male participants. Yoga exercises were taught to Parkinson's patients by a qualified yoga instructor. Improvements in toothbrushing skills were noted down by a single operator and oral hygiene status was analyzed using gingival index and plaque index on follow-up durations at 1, 2, 3, and 6 months. Yoga exercises comprised of warming up, stretching, yoga breathing exercises or pranayama, and/or relaxation process. Statistical analysis was performed by use of IBM SPSS Version 20.0. (IBM Corp., Armonk, NY) software designed for Windows. Intra-group comparison between categorical variables was done by statistical test-paired student 't-test'. RESULTS: On comparing plaque indices, the mean ± SD plaque index at 1st, 2nd, 3rd, and 6th months were 1.89 ± 0.02, 1.72 ± 0.01, 1.42 ± 0.12, and 0.56 ± 0.02, respectively. Mean ± SD gingival index scores at 1st month, 2nd month, 3rd month, and 6th-month durations, scores were 1.76 ± 0.06, 1.57 ± 0.12, 1.23 ± 0.02, and 0.76 ± 0.01, respectively. Statistical significance difference was noted on comparing the indices scores. CONCLUSION: Yoga practice has been shown to improve toothbrushing skills and oral hygiene in Parkinson's disease patients.

Contrastive learning in protein language space predicts interactions between drugs and protein targets.

Sequence-based prediction of drug-target interactions has the potential to accelerate drug discovery by complementing experimental screens. Such computational prediction needs to be generalizable and scalable while remaining sensitive to subtle variations in the inputs. However, current computational techniques fail to simultaneously meet these goals, often sacrificing performance of one to achieve the others. We develop a deep learning model, ConPLex, successfully leveraging the advances in pretrained protein language models ("PLex") and employing a protein-anchored contrastive coembedding ("Con") to outperform state-of-the-art approaches. ConPLex achieves high accuracy, broad adaptivity to unseen data, and specificity against decoy compounds. It makes predictions of binding based on the distance between learned representations, enabling predictions at the scale of massive compound libraries and the human proteome. Experimental testing of 19 kinase-drug interaction predictions validated 12 interactions, including four with subnanomolar affinity, plus a strongly binding EPHB1 inhibitor (KD = 1.3 nM). Furthermore, ConPLex embeddings are interpretable, which enables us to visualize the drug-target embedding space and use embeddings to characterize the function of human cell-surface proteins. We anticipate that ConPLex will facilitate efficient drug discovery by making highly sensitive in silico drug screening feasible at the genome scale. ConPLex is available open source at https://ConPLex.csail.mit.edu.

Therapeutic Role of Desmodium Species on its Isolated Flavonoids.

Secondary metabolites are an important part to play a major role in society and it was isolated from plant flavonoids and useful in the treatment of various kinds of diseases in the human race. They are widely used as food and nutrition supplements as well as antioxidants. Traditionally, the Desmodium species are an important tool for the secondary metabolites to treat various diseases. Desmodium triquetrum (Fabaceae) one of the Indian medicinal plants is widely used in the treatment of asthma and inflammation. Three flavonoids isolated from Desmodium triquetrum Linn namely Baicalein, Naringin and Neohesperidin are useful as antioxidants, food and nutrition supplements, that help the body to function efficiently while protecting it against toxins as well stressors. The role of flavonoids may be due to the presence of the phenolic compound. Similarly, the flavonoids such as gangetin, gangetinin, desmocarpin and desmodin isolated from the species Desmodium gangeticum are responsible for antileishmanial, antioxidant, anti-arthritic, and immunomodulatory activities. Additionally, isolated flavanoids from the species Desmodium triflorum show antibacterial, antiepileptic, antifungal, and radioprotective activities. So, the aim of the present study, based on the literature miming from the desmodium species is to acknowledge the importance of flavonoids in human health as dietary food supplements and therapeutic uses.

Assessment of the Role of Vitamin D in the Treatment of Oral Lichen Planus.

AIM: Lichen planus is an autoimmune disease that can affect the skin and mucous membranes, including the oral mucosa. Vitamin D plays a very important role in the bone health along with boosting immunity. This study was carried out to assess the role of vitamin D in the treatment of oral lichen planus. MATERIALS AND METHODS: A sample size of 450 was taken which included patients showing clinical presentation of oral lichen planus. The patients were equally divided into three different groups based on their vitamin D levels. The data were analyzed using SPSS version 26.0. RESULTS: The patients who were given the vitamin D supplementation showed the maximum improvement. The comparison of the data were found to be statistically significant. CONCLUSION: It was concluded that vitamin D played an important role in the treatment of oral lichen planus. CLINICAL SIGNIFICANCE: The role of vitamin D in lichen planus needs to be explored. This study may be useful in conducting further study to assess the role in vitamin D supplementation in the treatment of oral lichen planus.

Growth Factor and Intense Pulse Light in Flexor Tendon Repair: A Biomechanical Study at Strength and Gap Resistance.

BACKGROUND: Flexor tendon injuries are extremely common and they are usually the result of incised traumatic glass or knife injury. The process of tendon healing is a complicated and exceptionally-regimented mechanism that is originated and monitored by a vast number of diverse molecules. One of the most pivotal groups of mediators that are crucial to the healing process are growth factors (GF). Intense pulse light (IPL) can lead to evidence of new collagen formation with associated clinical improvement in tissue healing. The biological benefit of Intense pulse light (IPL) relies on judicious photothermolysis, where heat driven radiation is dissipated and focused at the cellular level. The aims of this study is to set out the effect of growth factor and IPL on healing following a tendon repair. METHODS: Bovine common digital extensor tendons (CDET) were used as an ex vivo model. 44 tendon repairs were performed by the lead author using 2.5 × magnification loupes and standard instruments. Clamped tendons were assigned into the following groups; control, IPL, GF, IPL and GF. After culturing, biomechanical testing was carried out using monotonic tensile testing with displacement-controlled uniaxial tension to failure. RESULTS: The mean values for ultimate tensile stress (UTS) for the control group was 53.51 N, for IPL it was 51.15 N, for growth factor was 70.10 N and for combined growth factor and IPL it was 75.16 N. CONCLUSIONS: This study showed significant improvement in UTS when repaired tendons were cultured with growth factor compared to control and IPL. This would suggest a biomechanical advantage for tendon healing.

Ecliptal, a promising natural lead isolated from Eclipta alba modulates adipocyte function and ameliorates metabolic syndrome.

A swift increase has been observed in the number of individuals with metabolic syndrome worldwide. A number of natural compounds have been identified towards combating metabolic syndrome. Adding to this premise, here we report the pleiotropic activities of Ecliptal (EC); a natural compound isolated from the herb Eclipta alba. Administration of EC was shown to have prominent anti-adipogenic effects in 3T3-L1 and hMSC derived adipocytes. It was shown to activate Wnt-pathway and alter AKT signaling. Additionally, it caused cell cycle arrest and inhibited mitotic clonal expansion. EC treatment augmented mitochondrial biogenesis as well as function as estimated by expression of PGC1α, UCP-1, mitochondrial complexes and estimation of oxygen consumption rate. EC also reduced LPS-induced inflammation and tunicamycin induced ER stress. Further, EC enhanced insulin sensitivity by increasing AKT phosphorylation, inhibiting PKCα/ßII phosphorylation and reducing leptin/adiponectin ratio. Finally, EC administration in Syrian golden hamsters was shown to have potent anti-dyslipidemic effects. Cumulatively, encompassing pleiotropic activities of EC, it could prove to be a potential drug candidate against obesity, insulin resistance and related metabolic syndrome.

Photo-bioreduction of Ag+ ions towards the generation of multifunctional silver nanoparticles: Mechanistic perspective and therapeutic potential.

In this article, light induced plant extract mediated one pot synthesis of silver nanoparticles (AgNPs) has been demonstrated and potential mechanistic insight in the synthesis has been investigated. Bioactive molecules containing medicinal plant Cassytha filiformis has been explored for the synthesis of silver nanoparticles. The as-synthesized silver nanoparticles were characterized by various analytical techniques including Ultraviolet-visible spectroscopy (UV-Vis), High Resolution Transmission Electron Microscopy (HR-TEM), Dynamic Light Scattering (DLS) and Fourier Transform Infrared Spectroscopy (FT-IR). Among different light sources (sunlight, room light, UV) applied the sunlight was found to be efficient external stimuli to induce rapid synthesis of AgNPs at room temperature. Modified DPPH assay indicated that polyphenolic compounds were most likely involved in the synthesis of AgNPs. Possible molecule responsible for the synthesis of AgNPs was identified, purified and characterized. Potential biomedical applications such as antibacterial, antifungal and anticancer activities of AgNPs have been evaluated. Irrespective of nature of pathogenic strains nanoparticles exhibited significant antibacterial activities against Gram positive (Streptococcus aureus) and Gram negative (Escherichia coli) bacterial pathogens. It showed higher activity on E. coli than on S. aureus. Distinct antifungal activity (MIC=5.244µg/ml) and remarkable anticancer activity (IC50=10µg/ml) was found against Candida albicans and HCT116 (colorectal carcinoma) cells, respectively. Taken together, these findings suggested that light induced plant generated silver nanoparticles could be used for various biomedical purposes.

Potential osteogenic activity of ethanolic extract and oxoflavidin isolated from Pholidota articulata Lindley.

ETHNOPHARMACOLOGICAL RELEVANCE: Pholidota articulata Lindley (PA) locally known as Hadjojen (bone jointer) belongs to family Orchidaceae is used for healing fractures in folklore tradition of Kumaon region of Uttarakhand, Himalaya, India. Bone is a dynamic organ and is constantly being remodeled in order to facilitate growth and repair. This process requires the involvement of bone forming osteoblast and bone resorbing osteoclast cells, which function in generating and mineralizing bone, giving strength and rigidity to the skeletal system. Present study was aimed to determine the therapeutic potential of ethanolic extract of PA and its isolated compound oxoflavidin, by characterizing their fracture healing properties. MATERIALS AND METHODS: Ovariectomized (Ovx) estrogen deficient adult female Balb/c mice were used for in vivo evaluation of osteogenic or bone healing potential of ethanolic extract of PA. Further, its isolated compounds were tested for their osteogenic efficacy using alkaline phosphatase assay and mineralization assay in vitro in mice calvarial osteoblasts. RESULTS: The ethanolic extract of PA exhibited significant restoration of trabecular micro-architecture in both femoral and tibial bones. Additionally, treatment with PA extract led to better bone quality and devoid of any uterine estrogenicity in ovariectomized estrogen deficient mice. One of the isolated compound, oxoflavidin enhanced ALP activity (a marker of osteoblast differentiation), mineral nodule formation and mRNA levels of osteogenic markers like BMP-2, Type 1 Collagen, RUNX-2 and osteocalcin. CONCLUSION: These results warrant that ethanolic extract of PA and it's pure compound oxoflavidin have fracture healing properties. The extract and oxoflavidin exhibit a strong threapeutical potential for the treatment and management of postmenopausal osteoporosis.

Cytoprotective and Anti-secretory Effects of Azadiradione Isolated from the Seeds of Azadirachta indica (neem) on Gastric Ulcers in Rat Models.

Azadirachta indica is well known medicinal plant mentioned in ancient herbal texts. It has been extensively used in Ayurvedic, Unani and Homoeopathic medicine and has become a luminary of modern medicine. As part of our drug discovery program we isolated azadiradione from the ethanolic extract of seeds of A. indica and evaluated for in-vivo antiulcer activity in cold restraint induced gastric ulcer model, aspirin induced gastric ulcer model, alcohol induced gastric ulcers model and pyloric ligation induced ulcer model. Azadiradione exhibited potent antiulcer activity through the inhibition of H+ K+-ATPase (proton pump) activity via its cytoprotective effect and also via its antisecretory effect. This combined effect has valuable potential in the future treatment of peptic ulceration.

In vitro anti-hyperglycemic activity of 4-hydroxyisoleucine derivatives.

The nonproteinogenic amino acid, 4-hydroxyisoleucine (1) has been isolated in large quantities from the fenugreek (T. foenum-graecum) seeds. Few novel derivatives (3-11 and 13-18) were prepared from the naturally occurring 4-hydroxyisoleucine (1) and screened for their in vitro glucose uptake stimulatory effect in L-6 skeletal muscle cells. The derivatives 6, 7, 8, 10 and 11 exhibited better glucose uptake stimulatory activity than parent compound, 4-hydroxyisoleucine at 5 and 10µM concentrations and compounds 7 and 11 enhanced translocation of insulin sensitive glucose transporters-4 in skeletal muscle cells.

Simple and effective method of heat therapy in lymphoedema.

Heat therapy is a well known conservative management for lymphoedema. We are describing here a heat therapy apparatus which is easy to make, cheap, transportable, easily reproducible and maintenance free and found to be very effective.

Synthesis of phosphorus esters by transesterification mediated by N-heterocyclic carbenes (NHCs).

The versatile nucleophilic organic catalysts N-heterocyclic carbenes (NHCs) have been shown to effectively mediate the transesterification of phosphorus esters under mild conditions; user-friendly imidazolium salts can also be employed as pre-catalysts.