COVID-19 fatality and DALYs, and associated metabolic disorders and ambient air pollutants in pre-Omicron era of the pandemic: an international comparative study.

BACKGROUND: Air pollution and a number of metabolic disorders have been reported to increase the risk of severe COVID-19 outcomes. This study explored the association between severe COVID-19 outcomes, metabolic disorders and environmental air pollutants, at regional level, across 38 countries. METHODS: We conducted an ecological study using COVID-19 data related to countries of the Organization for Economic Cooperation and Development (OECD), with an estimated population of 1.4 billion. They were divided into 3 regions: 1. Europe & Middle east; 2. Americas (north, central & south America); 3. East-Asia & West Pacific. The outcome variables were: COVID-19 case-fatality rate (CFR) and disability-adjusted life years (DALYs) at regional level. Freely accessible datasets related to regional DALYs, demographics and other environmental pollutants were obtained from OECD, WHO and the World in Data websites. Generalized linear model (GLM) was performed to determine the regional determinants of COVID-19 CFR and DALYs using the aggregate epidemiologic data (Dec. 2019-Dec. 2021). RESULTS: Overall cumulative deaths were 65,000 per million, for mean CFR and DALYs of 1.31 (1.2)% and 17.35 (2.3) years, respectively. Globally, GLM analysis with adjustment for elderly population rate, showed that COVID-19 CFR was positively associated with atmospheric PM2.5 level (beta = 0.64(0.0), 95%CI: 0.06-1.35; p < 0.05), diabetes prevalence (beta = 0.26(0.1), 95%CI: 0.12-0.41; p < 0.001). For COVID-19 DALYs, positive associations were observed with atmospheric NOx level (beta = 0.06(0.0), 95%CI: 0.02-0.82; p < 0.05) and diabetes prevalence (beta = 0.32(0.2), 95%CI: 0.04-0.69; p < 0.05). At regional level, adjusted GLM analysis showed that COVID-19 CFR was associated with atmospheric PM2.5 level in the Americas and East-Asia & Western Pacific region; it was associated with diabetes prevalence for countries of Europe & Middle east and East-Asia & Western Pacific region. Furthermore, COVID-19 DALYs were positively associated with atmospheric PM2.5 and diabetes prevalence for countries of the Americas only. CONCLUSION: These findings confirm that diabetes and air pollution increase the risk of disability and fatality due to COVID-19, with disparities in terms of their impact. They suggest that efficient preventive and management programs for diabetes and air pollution countermeasures would have curtailed severe COVID-19 outcome rates.

Phenylpropanoid-conjugated iridoid glucosides from leaves of Morinda morindoides.

Three phenylpropanoid-conjugated iridoid glucosides, acetylgaertneric acid (1), acetyldehydrogaertneroside (2), and dehydrogaertneric acid (10), together with nine known related iridoid glucosides (3-9, 11, and 12), two coumaroyl alkaloids, one benzenoid, and three flavonoid glucosides were isolated from leaves of Morinda morindoides (Rubiaceae). Structures of these isolated compounds were determined using spectroscopic analysis. Compounds 1-18 and previously isolated compounds (19-29) were evaluated for anti-trypanosomal activity against Trypanosoma cruzi Tulahuen strain (trypomastigote and amastigote) together with cytotoxicity against host cells, new-born mouse heart cells. Among them, molucidin (21) and prismatomerin (22) exhibited good anti-trypanosomal activity (IC50 of 4.67 and 5.70 µM, respectively), together with cytotoxicity (CC50 of 2.76 and 3.22 µM, respectively). Compounds 1-18 did not show anti-malarial activity against a chloroquine/mefloquine-sensitive strain of Plasmodium falciparum.

Rational quality assessment procedure for less-investigated herbal medicines: Case of a Congolese antimalarial drug with an analytical report.

Herbal medicines are the most globally used type of medical drugs. Their high cultural acceptability is due to the experienced safety and efficiency over centuries of use. Many of them are still phytochemically less-investigated, and are used without standardization or quality control. Choosing SIROP KILMA, an authorized Congolese antimalarial phytomedicine, as a model case, our study describes an interdisciplinary approach for a rational quality assessment of herbal drugs in general. It combines an authentication step of the herbal remedy prior to any fingerprinting, the isolation of the major constituents, the development and validation of an HPLC-DAD analytical method with internal markers, and the application of the method to several batches of the herbal medicine (here KILMA) thus permitting the establishment of a quantitative fingerprint. From the constitutive plants of KILMA, acteoside, isoacteoside, stachannin A, and pectolinarigenin-7-O-glucoside were isolated, and acteoside was used as the prime marker for the validation of an analytical method. This study contributes to the efforts of the WHO for the establishment of standards enabling the analytical evaluation of herbal materials. Moreover, the paper describes the first phytochemical and analytical report on a marketed Congolese phytomedicine.

Decreased thrombin activity by a Congolese herbal medicine used in sickle cell anemia.

ETHNOPHARMACOLOGICAL RELEVANCE: Aqueous extracts from Ceiba pentandra (Malvaceae/Bombacoideae) and Quassia africana (Simaroubaceae) are used as crude medicines for the management of sickle cell anemia (SCA) in the Democratic Republic of Congo (DR Congo). Since it is postulated that the pathogenesis of SCA is associated with an increased blood coagulation activity, the present study is conducted to determine the effect of the two extracts on the coagulation by assessing the thrombin activity and the plasma clotting time. MATERIALS AND METHODS: Thrombin activity was measured by chromogenic assay in the presence of the aqueous extracts (10, 100 or 200 µg/ml); and plasma clotting times were measured by activated partial thromboplastin time (APTT) and prothrombin time (PT) in the presence of C. pentandra (10, 100 or 200 µg/ml) and Q. africana (5, 20 or 50 µg/ml). RESULTS: Reduced thrombin activity and prolonged plasma clotting time measured by APTT were observed in the presence of C. pentandra extract only. However, plasma clotting time measured by PT was not modified by the use of the two extracts. CONCLUSIONS: This study suggests that the aqueous extract of C. pentandra may contain active components that reduce the thrombin activity and prolong the plasma clotting time by affecting the coagulation intrinsic pathway.

Effect of a Congolese herbal medicine used in sickle cell anemia on the expression of plasminogen activators in human coronary aortic endothelial cells culture.

ETHNOPHARMACOLOGICAL RELEVANCE: Aqueous extract of Ceiba pentandra, which is used for the management of sickle cell anemia (SCA) in DR Congo, exhibits antithrombin response by activation of Heparin cofactor II in vitro. This study examines the effect of the plant on the fibrinolytic activity to understand whether it can influence the coagulation-fibrinolysis system, since fibrinolysis disorder is one of the contributing causes of thrombotic crises in SCA. MATERIALS AND METHODS: Fibrinolysis proteins were determined by enzyme-immunoassay in the conditioned medium of cultured endothelial cells after treatment with the extract. Electrophoresis-zymography and RT-PCR tests were conducted to examine the activity and the RNA synthesis of these proteins, respectively. RESULTS: It was found that the extract decreased the activity of both tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor type-1 (PAI-1). However, it was revealed that this effect was not the result of an inhibition of their biosynthesis by endothelial cells. CONCLUSION: From the foregoing, it was revealed that the extract inhibited the secretion of the fibrinolytic proteins without affecting their synthesis by endothelial cells. Thus, the extract may not accelerate the digestion of fibrin clot resulting from thrombotic disorders in SCA.