Genomic analyses inform on migration events during the peopling of Eurasia.

High-coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record, and admixture between AMHs and Neanderthals predating the main Eurasian expansion, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago.

Antinociceptive principle from Curcuma aeruginosa.

BACKGROUND: The rhizome of Curcuma aeruginosa Roxb (Zingiberaceae) has been used as a traditional folk medicine for the treatment of rheumatic disorders in Bangladesh. The aim of the current study was the bioassay-guided isolation and purification of an antinociceptive principle from the methanol extract of C. aeruginosa rhizomes. METHODS: The antinociceptive activity was determined using acetic acid induced writhing and formalin induced licking in the Swiss albino mice to investigate central and peripheral antinociceptive principle of C. aeruginosa rhizomes. Vacuum Liquid Chromatography (VLC) and open column chromatography were used for separation. Crystallization was used for the purification of the isolated compound germacrone (1). Diclofenac (10 mg/kg) and aspirin (100 mg/kg) were used as positive control and 5% carboxymethyl cellulose (CMC) in distilled water (10 ml/kg) for negative control were used in the acetic acid induced writhing and formalin induced licking methods. RESULTS: The methanol extract exhibited 37.50 and 45.31% inhibition of writhing; 33.27 and 38.13% inhibition of licking in the first phase and 69.72, 73.71% inhibition of licking in the second phase at doses of 200 and 400 mg/kg, respectively. VLC of the extract yielded five fractions (Fr. 1 to Fr. 5). Fr. 1 exhibited 33.98% inhibition that was comparably higher than other fractions (Fr. 2 to Fr. 5) at a dose of 100 mg/kg. Column chromatography of Fr. 1 generated five fractions (SF. 1 to SF. 5). Fraction SF.3 exhibited 46.88% inhibition that was most potent among the other fractions at a dose of 50 mg/kg. Crystallization of the fraction SF.3 yielded germacrone (1), a cyclic sesquiterpene. Germacrone (1) showed 22.66, 34.77 and 51.17% inhibition of writhing at doses of 10, 20 and 40 mg/kg, respectively; 30.43 and 37.53% inhibition in the initial phase and 32.27 and 60.96% inhibition in the second phase of licking at doses of 200 and 400 mg/kg, respectively. CONCLUSION: Germacrone (1) showed a potent activity in both writhing and licking methods that indicates the compound as a central and peripheral antinociceptive principle of C. aeruginosa rhizomes with possible anti-inflammatory activity.

Analgesic principle from Curcuma amada.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Curcuma amada has been used as a folk medicine for the treatment of rheumatic disorders in the northern part of Bangladesh and has also used for the treatment of inflammation and fever in the Ayurvedic and Unani systems of medicine. Aim of the study was to investigate the analgesic principle of the MeOH extract of the rhizome of Curcuma amada by an in vivo bioassay guided chromatographic separation and purification, and the structure elucidation of the purified compound by spectroscopic methods. MATERIALS AND METHODS: Dried powder of Curcuma amada rhizomes was extracted with MeOH. The analgesic activity of the crude extract and its chromatographic fractions as well as the purified compound itself was evaluated by the acetic acid induced writhing method and the formalin induced licking test in Swiss albino mice. The MeOH extract was separated by chromatographic methods and the pure active compound was purified by crystallization in hexanes. The structure of the pure compound was then elucidated by spectroscopic methods. RESULTS: The MeOH extract of Curcuma amada exhibited 41.63% and 45.53% inhibitions in the acetic acid induced writhing method at doses of 200mg/kg and 400mg/kg, respectively. It also exerted 20.43% and 28.50% inhibitions in early phase at doses of 200mg/kg and 400mg/kg, respectively, and 30.41% and 42.95% inhibitions in late phase at doses of 200mg/kg and 400mg/kg, respectively in the formalin induced licking test. Vacuum Liquid Chromatography (VLC) of crude extract yielded five fractions and Fr. 1 was found to have the most potent analgesic activity with inhibitions of 36.96% in the acetic acid induced writhing method and 47.51% (early phase), 39.50% (late phase) in the formalin induced licking test at a dose of 200mg/kg. Column chromatography of Fr. 1 on silica gel generated seven fractions (SF. 1-SF. 7). SF. 2 showed the most potent activity with inhibition of 49.81% in the acetic acid induced writhing method at a dose of 100mg/kg. Crystallization of SF. 2 yielded (1) (zederone, 520mg). It showed statistically significant inhibitions of 38.91% and 52.14% in the acetic acid induced writhing method at doses of 20mg/kg and 40mg/kg, respectively. Moreover, it also showed statistically significant inhibitions of 27.79% and 29.93% (early phase) and of 38.24% and 46.08% (late phase) in the formalin induced licking test at doses of 20mg/kg and 40mg/kg, respectively. CONCLUSION: Isolation and characterization of zederone (1) as analgesic principle of Curcuma amada corroborate its use in Ayurvedic, Unani and folk medicines for the treatment of rheumatic disorders and also contributing to its pharmacological validation.

Antiulcer principle from Zingiber montanum.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhizome of Zingiber montanum has been extensively used as a folk medicine to ameliorate peptic ulcer at northern part of Bangladesh. AIM OF THE STUDY: To identify the antiulcer principle of the MeOH extract of the rhizome of Zingiber montanum by an ex vivo bioassay guided chromatographic separation and purification, and structure elucidation of the purified compound by spectroscopic methods. MATERIALS AND METHODS: Dried powder of Zingiber montanum rhizomes was extracted with MeOH. The antiulcer activity of the crude extract and its chromatographic fractions were evaluated by the inhibition of 1N HCl induced gastric lesions in Swiss albino mice. The pure compound was purified from the active fraction by crystallization with hexanes. Structure of the pure compound was elucidated by spectroscopic methods. The antiulcer activity of the pure compound was evaluated by the inhibition of 1N HCl, 95% ethanol and indomethacin induced gastric lesions in mice. RESULTS: The MeOH extract of Zingiber montanum showed 61.97% and 83.10% inhibition of the 1N HCl induced gastric lesions at doses of 200mg/kg and 400mg/kg, respectively, in mice. Chromatographic separation on silica gel of the extract was yielded seven fractions and the fraction 2 was found to have most potent antiulcer activity in mice. This fraction showed 77.46% inhibition of the 1N HCl induced gastric lesions at a dose of 40mg/kg in mice. Crystallization of the fraction yielded 1 (zerumbone, 180mg). It showed statistically 45.77% and 92.25% inhibition of 1N HCl induced gastric lesions in mice at doses of 20mg/kg and 40mg/kg, respectively. It also showed 29.07% and 45.35% inhibition of 95% ethanol induced gastric mucosal damage, and 64.76% and 72.38% inhibition of indomethacin induced gastric lesions in mice at doses of 20mg/kg and 40mg/kg, respectively. CONCLUSION: Zerumbone (1) showed potent cytoprotective effect against necrotizing agent (HCl) and non-steroidal anti-inflammatory drug (indomethacin) induced gastric ulceration. It also exhibited moderate cytoprotective effect against noxious agent (EtOH) induced gastric lesions. It can be considered as a promising new antiulcer natural drug lead.