A key focus in the field of drug discovery has been motivated by the neuroprotection of natural compounds. Cerebral ischemia is a multifaceted pathological process with a series of mechanisms, and a perspective for the development of neuroprotectants from traditional herbal medicine or natural products is a promising treatment for this disease. Natural compounds with the effects of anti-oxidation, anti-inflammation, anti-apoptosis, and neurofunctional regulation exhibit therapeutic effects on experimental ischemic brain injury. Conferring to the pharmacological mechanisms underlying neuroprotection, a study found that androgapholide, a diterpene lactone compound, exhibits varying degrees of neuroprotective activities in both in vitro and in vivo experimental models of stroke. The neuroprotective mechanisms of andrographolide are suggested as: (I) increasing nuclear factor E2-related factor 2-heme oxygenase (Nrf2-HO-1) expression through p38-mitogen activated protein kinase (MAPK) regulation, (II) inducing cerebral endothelial cells (CEC) apoptosis and caspase-3 activation, (III) down regulating Bax, inducible nitric oxide synthase (iNOS), and (IV) inhibiting hydroxyl radical (OH−) formation, and activating transcription factor NF-κB signaling pathways. Recently, several researchers have also been trying to unveil the principal mechanisms involved in the neuroprotective effects of andrographolide. Therefore, this review aims to summarize an overview on the neuroprotective effects of andrographolide and exemplifies the essential mechanisms involved. This paper can provide information that andrographolide drug discovery may be a promising strategy for the development of a novel class of neuroprotective drug.

In oncotherapy, ruthenium (Ru) complexes are reflected as potential alternatives for platinum compounds and have been proved as encouraging anticancer drugs with high efficacy and low side effects. Cardiovascular diseases (CVDs) are mutually considered as the number one killer globally, and thrombosis is liable for the majority of CVD-related deaths. Platelets, an anuclear and small circulating blood cell, play key roles in hemostasis by inhibiting unnecessary blood loss of vascular damage by making blood clot. Platelet activation also plays a role in cancer metastasis and progression. Nevertheless, abnormal activation of platelets results in thrombosis under pathological settings such as the rupture of atherosclerotic plaques. Thrombosis diminishes the blood supply to the heart and brain resulting in heart attacks and strokes, respectively. While currently used anti-platelet drugs such as aspirin and clopidogrel demonstrate efficacy in many patients, they exert undesirable side effects. Therefore, the development of effective therapeutic strategies for the prevention and treatment of thrombotic diseases is a demanding priority. Recently, precious metal drugs have conquered the subject of metal-based drugs, and several investigators have motivated their attention on the synthesis of various ruthenium (Ru) complexes due to their prospective therapeutic values. Similarly, our recent studies established that novel ruthenium-based compounds suppressed platelet aggregation via inhibiting several signaling cascades. Our study also described the structure antiplatelet-activity relationship (SAR) of three newly synthesized ruthenium-based compounds. This review summarizes the antiplatelet activity of newly synthesized ruthenium-based compounds with their potential molecular mechanisms.

This paper addresses the linehaul-feeder vehicle routing problem with virtual depots and time windows LFVRPTW . Small and large vehicles deliver services to customers within time constraints; small vehicles en route may reload commodities from either the physical depot or from the larger vehicle at a virtual depot before continuing onward. A two-stage solution heuristic involving Tabu search is proposed to solve this problem. The test results show that the LFVRPTW performs better than the vehicle routing problem with time windows in terms of both objective value and the number of small vehicles dispatched.