humulene and Malaria

The FDA approved drug Dronabinol was identified in a previous study applying virtual screening using the haemozoin crystal as a target against malaria parasites. The active ingredient of dronabinol is synthetic tetrahydrocannabinol (THC), which is one of the major cannabinoids from Cannabis sativa. Traditional use of cannabis for malaria fever was reported in the world's oldest pharmacopoeia, dating to around 5000 years ago. In this research we report that THC inhibits β-haematin (synthetic haemozoin) and malaria parasite growth. Due the psychoactivity of THC, CBD, the other major naturally occurring cannabinoid that lacks the off-target psychoactive effects of THC, was also tested and inhibited β-haematin but showed only a mild antimalarial activity. To evaluate whether THC inhibit haemozoin formation, we performed a cellular haem fractionation assay that indicated that is not the likely mechanism of action. For the first time, the cannabinoid chemical structure is raised as a new chemical class to be further studied for malaria treatment, aiming to overcome the undesirable psychoactive effects of THC and optimize the antimalarial effects.

Topics: Antimalarials; Cannabis; Dose-Response Relationship, Drug; Dronabinol; Hemeproteins; HL-60 Cells; Humans; Malaria; Molecular Structure; Parasitic Sensitivity Tests; Plasmodium falciparum; Structure-Activity Relationship

Mosquitoes (Diptera: Culicidae) are important vectors of terms of public health relevance, especially in tropical and sub-tropical regions. The continuous and indiscriminate use of conventional pesticides for the control of mosquito vectors has resulted in the development of resistance and negative impacts on non-target organisms and the environment. Therefore, there is a need for development of effective mosquito control tools. In this study, the larvicidal and repellent activity of Zingiber nimmonii rhizome essential oil (EO) was evaluated against the malaria vector Anopheles stephensi, the dengue vector Aedes aegypti, and the lymphatic filariasis vector Culex quinquefasciatus. The chemical composition of the EO was analyzed by gas chromatography-mass spectroscopy (GC-MS). GC-MS revealed that the Z. nimmonii EO contained at least 33 compounds. Major constituents were myrcene, β-caryophyllene, α-humulene, and α-cadinol. In acute toxicity assays, the EO showed significant toxicity against early third-stage larvae of An. stephensi, Ae. aegypti, and Cx. quinquefasciatus, with LC50 values of 41.19, 44.46, and 48.26 μg/ml, respectively. Repellency bioassays at 1.0, 2.0, and 5.0 mg/cm(2) of Z. nimmonii EO gave 100 % protection up to 120, 150, and 180 min. against An. stephensi, followed by Ae. aegypti (90, 120, and 150 min) and Cx. quinquefasciatus (60, 90, and 120 min). Furthermore, the EO was safer towards two non-target aquatic organisms, Diplonychus indicus and Gambusia affinis, with LC50 values of 3241.53 and 9250.12 μg/ml, respectively. Overall, this research adds basic knowledge to develop newer and safer natural larvicides and repellent from Zingiberaceae plants against malaria, dengue, and filariasis mosquito vectors.

Topics: Acyclic Monoterpenes; Aedes; Alkenes; Animals; Anopheles; Culex; Dengue; Elephantiasis, Filarial; Gas Chromatography-Mass Spectrometry; Insect Repellents; Insecticides; Larva; Malaria; Monocyclic Sesquiterpenes; Monoterpenes; Mosquito Control; Mosquito Vectors; Oils, Volatile; Plant Leaves; Polycyclic Sesquiterpenes; Sesquiterpenes; Terpenes; Zingiberaceae

Illnesses related to both the pharmacologic properties of abused substances and their methods of administration often bring the teenager to medical attention and may provide sufficient motivation for the adolescent to seek help beyond the acute problem. Successful treatment of an overdose reaction, an abstinence syndrome, or any other medical complication of drug abuse may give the physician a unique opportunity to begine further evalution for future care.

Topics: Adolescent; Aerosols; Alcohol Drinking; Amphetamines; Bacterial Infections; Cannabis; Embolism; Female; Hallucinogens; Hepatitis A; Humans; Hypnotics and Sedatives; Malaria; Male; Opium; Pharmaceutical Preparations; Poisoning; Substance Withdrawal Syndrome; Substance-Related Disorders