Potential biomedical applications of Araucaria araucana as an antispasmodic, bronchodilator, vasodilator, and antiemetic: Involvement of calcium channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Since pre-Columbian era, the resin of Araucaria araucana tree has been used traditionally for the treatment of ulcers and wounds. Araucaria species have also been used to treat inflammation, respiratory problems, viral infections, ulcers, and rheumatoid, cardiovascular, and neurological disorders. AIMS AND OBJECTIVE: Due to its popular use, the authors aimed to scrutinize the potential of this plant as an antispasmodic and an antiemetic agent. Furthermore broncho- and vasodilatory effects of this plant was explored to rationalize its folkloric uses. MATERIALS AND METHODS: Araucaria araucana crude extract (Aa.Cr) was evaluated in isolated preparations of rabbit jejunum, trachea, aorta, and atria to investigate the antispasmodic, bronchodilator, and vasodilator effects. The potential mechanistic approaches were compared with the standard drug 'verapamil'. The antiemetic activity was determined and compared with the standard drug 'domperidone' via chick emesis model. RESULTS: Aa.Cr dose-dependently relaxed both spontaneous and K+-induced contractions in the isolated jejunum preparations of rabbits. In concentration-response curves of calcium (Ca++), Aa.Cr also triggered the rightward shift like verapamil. Applying carbachol and phenylephrine (1 µM) and K+ (80 mM) to the isolated tracheal and aortic tissue preparation, respectively, resulted in broncho- and vasodilatory activities, respectively which may be due to the inhibition of Ca++ channels. Aa.Cr inhibited atrial force and spontaneous contractions in the rabbit's right atria. Aa.Cr exhibited significant antiemetic activity (P < 0.001 vs. saline) in dose-dependent (50-150 mg/kg) manner like domperidone. In silico molecular docking was performed to investigate the biological targets of purified components of Aa.Cr which revealed that cadinol dominantly targets ß2 receptors to cause bronchodilation, however, eudesmin binds non-specifically to all the selected targets, while secoisolariciresinol mediated high hydrogen bonding with muscarinic receptors (M1 and M3) and Ca++ channels, thus shows the suggested mechanistic pathways of targeted activities. CONCLUSIONS: The results of this study indicates that Aa.Cr may exhibit antispasmodic activity, bronchodilation, and vasodilation by inhibiting voltage-dependent Ca++ channels and release of subcellular calcium. This explains its folkloric use in hypertension, bronchospasms, gastrointestinal spasms, and emesis.

Role of Plant-Derived Active Constituents in Cancer Treatment and Their Mechanisms of Action.

Despite significant technological advancements in conventional therapies, cancer remains one of the main causes of death worldwide. Although substantial progress has been made in the control and treatment of cancer, several limitations still exist, and there is scope for further advancements. Several adverse effects are associated with modern chemotherapy that hinder cancer treatment and lead to other critical disorders. Since ancient times, plant-based medicines have been employed in clinical practice and have yielded good results with few side effects. The modern research system and advanced screening techniques for plants' bioactive constituents have enabled phytochemical discovery for the prevention and treatment of challenging diseases such as cancer. Phytochemicals such as vincristine, vinblastine, paclitaxel, curcumin, colchicine, and lycopene have shown promising anticancer effects. Discovery of more plant-derived bioactive compounds should be encouraged via the exploitation of advanced and innovative research techniques, to prevent and treat advanced-stage cancers without causing significant adverse effects. This review highlights numerous plant-derived bioactive molecules that have shown potential as anticancer agents and their probable mechanisms of action and provides an overview of in vitro, in vivo and clinical trial studies on anticancer phytochemicals.

An Updated List of Neuromedicinal Plants of Pakistan, Their Uses, and Phytochemistry.

BACKGROUND: Almost every region of Pakistan is stacked with a large number of medicinal plants. Due to high cost and unavailability of allopathic medicines for the neurological diseases, especially in rural areas, traditional healers prescribe phytotherapy for various neurological diseases like epilepsy, depression, anxiety, insomnia, Alzheimer, and migraine. Such treatments are considered to be most effective by the native people. METHODS: The data was collected from articles published on medicinal plants of various districts of Pakistan, using article search engines like Medline, Pubmed, Web of Science, Science Direct, and Google Scholar. Also, information regarding various neurological uses and mode of applications of medicinal plants was obtained from traditional healers, folk medicine users, and local elderly people having knowledge of medicinal plants. RESULTS: A total of 54 families were found to be used in various neurological diseases, of which the highest use was of Solanaceae (22.22%), Asteraceae (12.96%), Lamiaceae, Papaveraceae, and Poaceae, 9% each, and Caprifoliaceae, Cucurbitaceae, Rhamnaceae, and Rosaceae, 5.5% each. According to districts, 15% of plants that were effective in neurological affections were found in Bahawalpur, 11% in Swat, 8% in Muzaffarabad, 7% in Malakand, and 6% in Bahawalnagar, Dir, Gilgat, and Sarghoda each, with 5% in Dera ghazi khan and Jhelum each. According to the plant's habit, out of total of 103 plants, 61.15% were found to be herbs, 22.33% trees, 11.65% shrubs, and 4.85% climbers. According to the part used of plant, whole plant, leaves, fruits, roots, seeds, and flowers were found to be used 32.03%, 24.27%, 20.38%, 16.50%, 13.59%, and 11.65%, respectively. According to disease's types, 45.63% were found to be effective in insomnia, 31.06% in epilepsy 12.62% in depression, 6.80% in anxiety, 7.77% in hysteria, and 5.88% in migraine. CONCLUSION: Taking into consideration this useful knowledge on medicinal properties of the plants for curing neurologic diseases, it is believed that research in areas of ethnomedicine and ethnopharmacology can bring auspicious results that have potential of adding value to the very rich natural resources of Pakistan. This study will help all the researchers from diverse backgrounds working on plants based medicine for neurological diseases.