Preclinical techniques for drug discovery in psoriasis.

Psoriasis is a chronic, inflammatory, papulosquamous, noncontagious disease characterized by scaly, demarcated erythematous plaque, affecting skin, nails, and scalp. The IL-23/Th17 axis is the main operator in the development of psoriasis. Psoriasis is affecting worldwide, and new treatment options are urgently needed. Various local and systemic treatments are available for psoriasis but they only provide symptomatic relief because of numerous unknown mechanisms. Clinical trials demand overwhelming resources; therefore, drug development predominantly depends on the in-vivo, in-vitro, and ex-vivo techniques. Immediate attention is required to develop experimental techniques that completely imitate human psoriasis to assist drug development. This review portrays the various in-vivo, in-vitro, and ex-vivo techniques used in psoriasis research. It describes these techniques' characteristics, pathological presentations, and mechanisms. The experimental techniques of psoriasis provide significant information on disease progression mechanisms and possible therapeutic targets. However, until now, it has been challenging to invent a timely, affordable model that precisely imitates a human disease. Only the xenotransplantation model is reckoned as the closer, that mimics the complete genetic, and immunopathogenic event. Imiquimod-induced psoriasis and HaCat cell lines are popular among researchers because of their convenience, ease of use, and cost-effectiveness. There need to further improve the experimental techniques to best serve the disease imitation and meet the research goal.

Evaluation of acute intravenous toxicity of HEPES: Is Good's buffer good and safe enough for clinical utilization in nuclear medicine?

OBJECTIVE: Good's buffer or HEPES has advantages over other buffers commonly used in radiopharmaceutical preparation as it exhibits significantly lower complexation tendency with metal ions. However, use of HEPES buffer for radiolabeling reactions, meant for clinical applications, has been underrated due to the non-availability of sufficient toxicity data. The objective of the present study is to find the evidences towards safety of intravenous administration of HEPES through systemic toxicological studies in small animal model to support its safe application for clinical exploitation. EXPERIMENTAL: A pilot study was performed to investigate the lethal dose of HEPES in female Sprague Dawley rats by administering seven different doses of HEPES solution (150 to 2000 mg/kg), through intravenous pathway. Similarly, for determining maximum tolerated dose (MTD), gradually increasing doses of HEPES (50 to 950 mg/kg) were administered in the same species via similar pathway. Various hematological and clinical pathological investigations were carried out in order to find out the safe administration dose of HEPES in rats. RESULTS: No mortality was observed up to 2000 mg/kg doses of HEPES. The doses beyond 300 mg/kg resulted few temporary adverse effects, though these were found to disappear within 4-5 days of dosing. CONCLUSION: The amount of HEPES to be administered during clinical intervention is usually much lower (typically 1-2.5 mg per kg of body weight of healthy adult) than the MTD determined in rat model during present report. Hence, the utilization of this buffer for preparation of radiolabeled drugs for human investigation may be safe. However, further detailed investigations may be warranted for supporting the candidature of Good's buffer for regular clinical exploitation.

Hypericum perforatum: a comprehensive review on pharmacognosy, preclinical studies, putative molecular mechanism, and clinical studies in neurodegenerative diseases.

The herb Hypericum perforatum, also referred to as St. John's wort, has drawn a lot of interest because of its potential therapeutic benefits in treating neurodegenerative illnesses. Due to the absence of effective therapies, illnesses like Alzheimer's and Parkinson's disease pose an increasing worldwide health concern. Because of its wide variety of phytochemicals, especially hyperforin, and hypericin, Hypericum perforatum is well known for its neuroprotective properties. These substances have proven to be able to affect different cellular processes linked to neurodegeneration. They can act as anti-inflammatory, antioxidant, and neurotransmitter system regulators, which may help halt neurodegenerative illnesses' progression. The use of Hypericum perforatum extracts and its contents has shown encouraging results in research on animal models of neurodegenerative disorders. These advantages include higher nerve cell survival, lowered oxidative stress, and higher cognitive performance. Underscoring its versatile potential to combat neurodegeneration, Hypericum perforatum has neuroprotective mechanisms that modulate neuroinflammation and prevent apoptotic pathways. In conclusion, Hypericum perforatum shows tremendous promise as a potential treatment for neurological illnesses due to its wide variety of phytochemicals. To completely comprehend its specific mechanisms of action and turn these discoveries into efficient clinical therapies, additional research is needed. Investigating Hypericum perforatum's function in neurodegenerative disorders may present new opportunities for the advancement of ground-breaking therapeutic strategies.

Infrequent use of medicinal plants from India in snakebite treatment.

Snakes have fascinated humankind for millennia. Snakebites are a serious medical, social, and economic problem that are experienced worldwide; however, they are most serious in tropical and subtropical countries. The reasons for this are 1) the presence of more species of the most dangerous snakes, 2) the inaccessibility of immediate medical treatment, and 3) poor health care. The goal of this study was to collect information concerning rare, less utilized, and less studied medicinal plants. More than 100 plants were found to have potential to be utilized as anti-snake venom across India. Data accumulated from a variety of literature sources revealed useful plant families, the parts of plants used, and how to utilize them. In India, there are over 520 plant species, belonging to approximately 122 families, which could be useful in the management of snakebites. This study was conducted to encourage researchers to create herbal antidotes, which will counteract snake venom. These may prove to be an inexpensive and easily assessable alternative, which would be of immense importance to society. Plants from families such as Acanthaceae, Arecaceae, Apocynaceae, Caesalpiniaceae, Asteraceae, Cucurbitaceae, Fabaceae, Euphorbiaceae, Lamiaceae, Rubiaceae, and Zingiberaceae are the most useful. In India, experts of folklore are using herbs either single or in combination with others.