Targeting potentially active compounds from Psidium guajava L. collected from Lao PDR against the Neglected Tropical Diseases using a metabolomic approach

Les maladies tropicales négligées (MTN) sont l'une des principales préoccupations de santé publique pour leur impact négatif sur la santé et l'économie de nombreux pays, notamment en République Démocratique Populaire du Laos. Parmi ces maladies, la dengue et la leishmaniose ont suscité l'intérêt des pouvoirs publics en raison d'incidences estimées à 50 à 100 millions et 1 million respectivement. En outre, les traitements disponibles pour ces maladies ne sont pas efficaces en raison de leur manque de spécificité, de leur toxicité, de phénomènes de résistance et de leurs coûts prohibitifs au regard des populations. Le Laos est une source importante de plantes médicinales avec une couverture forestière de plus de 45% de la surface du pays. Parmi ces plantes Psidium guajava a été décrites pour ses propriétés anti-dengue et antileishmanique. Au cours de ces travaux, nous avons mis en œuvre des approches métabolomiques afin d'identifier les composés responsables de ces propriétés. Plusieurs extraits bruts de feuilles de P. guajava récoltées dans différentes régions du Laos ont été profilés par chromatographie liquide couplée à la spectrométrie de masse à haute résolution et évalués pour leurs propriétés anti-dengue et antileishmaniques. Les résultats ont montré que la fraction moins polaire de P. guajava était la plus active à la fois pour la dengue et la Leishmania (environ 70% d'inhibition dans le DENV-2 à 10µg/mL et plus de 50% d'inhibition à 25µg/mL pour la Leishmania). L'analyse des données multivariées de la fraction moins polaire a mis en évidence une famille de composés triterpéniques, dont l'acide jacoumarique (antidengue et antileishmanien) et l'acide corosolique (antileishmanien).Neglected Tropical Diseases (NTD) are the main public health concern that caused a negative impact on the health and economy of many developing countries particularly in Lao People's Democratic Republic. Dengue and Leishmaniasis diseases have an estimated annual case of 50-100 million and 1 million, respectively. In addition, available treatments for these diseases are not sufficient because of lack of specificity, toxicity issue, drug resistance, and treatment cost. As Lao PDR has a huge source of herbal medicine, investigation of anti-dengue and antileishmanial potential plants is of utmost interest. According to previous studies on Psidium guajava on neglected tropical disease, guava was reported about anti-dengue and antileishmanial activities from crude bark and leaves extracts. In order to target active compounds from crude guava extract, a metabolomic based workflow has been set-up. Several P. guajava leaves were harvested from different locations in Lao PDR and profiled by liquid chromatography coupled to high resolution mass spectrometry. Additionally, each extract was evaluated for their anti-dengue and antileishmanial activities. The results showed that the less polar fraction from P. guajava was the most active both in dengue and Leishmania (about 70% inhibition in DENV-2 at 10µg/mL and more than 50% inhibition at 25µg/mL in Leishmania). Multivariate data analyses of the less polar fraction highlighted a family of triterpenoid compounds, including jacoumaric acid (anti-dengue and antileishmanial activities) and corosolic acid (antileishmanial activity)

Antileishmanial Compounds Isolated from Psidium Guajava L. Using a Metabolomic Approach

With an estimated annual incidence of one million cases, leishmaniasis is one of the top five vector-borne diseases. Currently available medical treatments involve side effects, including toxicity, non-specific targeting, and resistance development. Thus, new antileishmanial chemical entities are of the utmost interest to fight against this disease. The aim of this study was to obtain potential antileishmanial natural products from Psidium guajava leaves using a metabolomic workflow. Several crude extracts from P. guajava leaves harvested from different locations in the Lao People’s Democratic Republic (Lao PDR) were profiled by liquid chromatography coupled to high-resolution mass spectrometry, and subsequently evaluated for their antileishmanial activities. The putative active compounds were highlighted by multivariate correlation analysis between the antileishmanial response and chromatographic profiles of P. guajava mixtures. The results showed that the pooled apolar fractions from P. guajava were the most active (IC50 = 1.96 ± 0.47 µg/mL). Multivariate data analysis of the apolar fractions highlighted a family of triterpenoid compounds, including jacoumaric acid (IC50 = 1.318 ± 0.59 µg/mL) and corosolic acid (IC50 = 1.01 ± 0.06 µg/mL). Our approach allowed the identification of antileishmanial compounds from the crude extracts in only a small number of steps and can be easily adapted for use in the discovery workflows of several other natural products

Identification des composés potentiellement actifs de Psidium guajava L. collectés au Laos vis-à-vis de maladies tropicales négligées en utilisant des approches métabolomiques

Les maladies tropicales négligées (MTN) sont l'une des principales préoccupations de santé publique pour leur impact négatif sur la santé et l'économie de nombreux pays, notamment en République Démocratique Populaire du Laos. Parmi ces maladies, la dengue et la leishmaniose ont suscité l'intérêt des pouvoirs publics en raison d'incidences estimées à 50 à 100 millions et 1 million respectivement. En outre, les traitements disponibles pour ces maladies ne sont pas efficaces en raison de leur manque de spécificité, de leur toxicité, de phénomènes de résistance et de leurs coûts prohibitifs au regard des populations. Le Laos est une source importante de plantes médicinales avec une couverture forestière de plus de 45% de la surface du pays. Parmi ces plantes Psidium guajava a été décrites pour ses propriétés anti-dengue et antileishmanique. Au cours de ces travaux, nous avons mis en œuvre des approches métabolomiques afin d'identifier les composés responsables de ces propriétés. Plusieurs extraits bruts de feuilles de P. guajava récoltées dans différentes régions du Laos ont été profilés par chromatographie liquide couplée à la spectrométrie de masse à haute résolution et évalués pour leurs propriétés anti-dengue et antileishmaniques. Les résultats ont montré que la fraction moins polaire de P. guajava était la plus active à la fois pour la dengue et la Leishmania (environ 70% d'inhibition dans le DENV-2 à 10µg/mL et plus de 50% d'inhibition à 25µg/mL pour la Leishmania). L'analyse des données multivariées de la fraction moins polaire a mis en évidence une famille de composés triterpéniques, dont l'acide jacoumarique (antidengue et antileishmanien) et l'acide corosolique (antileishmanien).Neglected Tropical Diseases (NTD) are the main public health concern that caused a negative impact on the health and economy of many developing countries particularly in Lao People's Democratic Republic. Dengue and Leishmaniasis diseases have an estimated annual case of 50-100 million and 1 million, respectively. In addition, available treatments for these diseases are not sufficient because of lack of specificity, toxicity issue, drug resistance, and treatment cost. As Lao PDR has a huge source of herbal medicine, investigation of anti-dengue and antileishmanial potential plants is of utmost interest. According to previous studies on Psidium guajava on neglected tropical disease, guava was reported about anti-dengue and antileishmanial activities from crude bark and leaves extracts. In order to target active compounds from crude guava extract, a metabolomic based workflow has been set-up. Several P. guajava leaves were harvested from different locations in Lao PDR and profiled by liquid chromatography coupled to high resolution mass spectrometry. Additionally, each extract was evaluated for their anti-dengue and antileishmanial activities. The results showed that the less polar fraction from P. guajava was the most active both in dengue and Leishmania (about 70% inhibition in DENV-2 at 10µg/mL and more than 50% inhibition at 25µg/mL in Leishmania). Multivariate data analyses of the less polar fraction highlighted a family of triterpenoid compounds, including jacoumaric acid (anti-dengue and antileishmanial activities) and corosolic acid (antileishmanial activity)

Antileishmanial compounds isolated from Psidium guajava L. using a metabolomic approach

With an estimated annual incidence of one million cases, leishmaniasis is one of the top five vector-borne diseases. Currently available medical treatments involve side effects, including toxicity, non-specific targeting, and resistance development. Thus, new antileishmanial chemical entities are of the utmost interest to fight against this disease. The aim of this study was to obtain potential antileishmanial natural products from Psidium guajava leaves using a metabolomic workflow. Several crude extracts from P. guajava leaves harvested from different locations in the Lao People's Democratic Republic (Lao PDR) were profiled by liquid chromatography coupled to high-resolution mass spectrometry, and subsequently evaluated for their antileishmanial activities. The putative active compounds were highlighted by multivariate correlation analysis between the antileishmanial response and chromatographic profiles of P. guajava mixtures. The results showed that the pooled apolar fractions from P. guajava were the most active (IC50 = 1.96 +/- 0.47 mu g/mL). Multivariate data analysis of the apolar fractions highlighted a family of triterpenoid compounds, including jacoumaric acid (IC50 = 1.318 +/- 0.59 mu g/mL) and corosolic acid (IC50 = 1.01 +/- 0.06 mu g/mL). Our approach allowed the identification of antileishmanial compounds from the crude extracts in only a small number of steps and can be easily adapted for use in the discovery workflows of several other natural products

A metabolomic approach to identify anti-hepatocarcinogenic compounds from plants used traditionally in the treatment of liver diseases

International audienceLiver cancer is a major health burden in Southeast Asia, and most patients turn towards the use of medicinal plants to alleviate their symptoms. The aim of this work was to apply to Southeast Asian plants traditionally used to treat liver disorders, a successive ranking strategy based on a comprehensive review of the literature and metabolomic data in order to relate ethnopharmacological relevance to chemical entities of interest. We analyzed 45 publications resulting in a list of 378 plant species, and our point system based on the frequency of citation in the literature allowed the selection of 10 top ranked species for further collection and extraction. Extracts of these plants were tested for their in vitro anti-proliferative activities on HepG2 cells. Ethanolic extracts of Andrographis paniculata, Oroxylum indicum, Orthosiphon aristatus and Willughbeia edulis showed the highest anti-proliferative effects (IC50 = 195.9, 64.1, 71.3 and 66.7 μg/ml, respectively). A metabolomic ranking model was performed to annotate compounds responsible for the anti-proliferative properties of A. paniculata (andrographolactone and dehydroandrographolide), O. indicum (baicalein, chrysin, oroxylin A and scutellarein), O. aristatus (5-desmethylsinensetin) and W. edulis (parabaroside C and procyanidin). Overall, our dereplicative approach combined with a bibliographic scoring system allowed us to rapidly decipher the molecular basis of traditionally used medicinal plants

Hmong herbal medicine and herbalists in Lao PDR: pharmacopeia and knowledge transmission

International audienceBackground: In Lao PDR, the Hmong ethnic group has extensive knowledge about the use of medicinal plants. However, despite the importance of the Hmong pharmacopeia as a primary health care resource, no study has been undertaken to thoroughly document medicinal plant knowledge and its transmission. Objectives of this study are (i) to describe and characterize Hmong pharmacopeia, and (ii) to understand how medicinal plant knowledge is transmitted and spread among Hmong in Lao PDR, in order to assess whether this knowledge base is under threat. Methods: In order to describe Hmong pharmacopeia, a total of 14 interlocutors were interviewed in three provinces (Bokeo, Xieng Khouang, and Vientiane), using "walk in the wood" methodology. To gain insight about knowledge transmission, semi-structured interviews were conducted with 28 people. Twenty of them were herbalists. Data analysis was performed using univariate analysis for the description of the pharmacopeia. Medicinal plant knowledge consistency was assessed through use and plant name overlapping. Answers to the semi-structured interview on knowledge transmission were analyzed qualitatively.Results: Three hundred thirty-three different medicinal species were collected. The majority of uses attributed to plants were gastrointestinal conditions (22% of total use reports), gynecological conditions and sexually transmitted disease (12%), skin affections (8%), kidney and bladder problems (5%), physical traumas (5%), and aphrodisiac (or male tonics; 5%). Use convergences are more marked in the gynecological sphere, but there is a strong heterogeneity in practices and knowledge. Medicinal plant knowledge transmission is oral, gained from direct experience since childhood, matrilineal, and kept strictly within the family lineage. Apparent limited consensus on uses might stem from the method of knowledge transmission and to the economic value given to medicinal plants. Discussion: Use pattern of species from the Hmong pharmacopeia does not appear to be strikingly different from the national Lao pharmacopeia. Differences may lie in the methods and reasons for knowledge transmission. It can be proposed that the economic value given to plants helps in keeping the knowledge alive, and encourages its transmission.Conclusion: Hmong traditional medicine is constantly evolving in a dynamic process and aims to respond to health problems faced by the local population. Herbalists appear as health fully fledged actors and should be recognized and valued as such