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

Chassagne, François; Haddad, Mohamed; Amiel, Aurélien; Phakeovilay, Chiobouaphong; Manithip, Chanthanom; Bourdy, Geneviève; Deharo, Eric; Marti, Guillaume

doi:10.1016/j.fitote.2018.02.021

Cited by 41 publications

(25 citation statements)

References 43 publications

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“…Whole-dried plants of Phyllanthus niruri (Bhuiamla) and Andrographis paniculata (Kalmegh), along with roots of Tephrosia purpurea (Sharapunkha) and Boerhavia diffusa (Punarnava), were used. All four herbs individually, or in combination of one or two, are being used in Ayurveda for several hundred years for gastrointestinal, liver, spleen, and renal disorders [19][20][21]. To our knowledge, this is the first combination of these four plants.…”

Section: Introductionmentioning

confidence: 99%

Hepatoprotective Activity of BV‐7310, a Proprietary Herbal Formulation of Phyllanthus niruri, Tephrosia purpurea, Boerhavia diffusa, and Andrographis paniculata, in Alcohol‐Induced HepG2 Cells and Alcohol plus a Haloalkane, CCl₄, Induced Liver Damage in Rats

Dey¹,

Chaskar²,

Bhatt³

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Excessive alcohol consumption is a worldwide threat with severe morbidity and mortality. Other than abstinence, there is still no FDA-approved drug for alcoholic liver disease (ALD). Liver is the primary site of ethanol metabolism and hence gets the most damage from excessive drinking. It triggers multiple signalling events including inflammation, leading to an array of hepatic lesions like steatosis, hepatitis, fibrosis, and cirrhosis. Similarly, when medications or xenobiotic compounds are ingested orally, the liver gets the highest exposure of those metabolites, which in turn can cause severe liver toxicity. BV-7310 is a standardized mixture of four Ayurvedic plants, namely, Phyllanthus niruri, Tephrosia purpurea, Boerhavia diffusa, and Andrographis paniculata. In different systems of traditional medicine, each of these plants has been known to have use in gastrointestinal disorders. We wanted to assess the combined effect of these plant extracts on alcohol-induced liver damage. First, we investigated the hepatoprotective activity of BV-7310 against alcohol-induced toxicity in human liver HepG2 cells. Ethanol treatment (120 mM for 48 hours) significantly showed toxicity (around 42%) in these cells, and coincubation with BV-7310 prevented ethanol-induced cell death in a dose-dependent manner. Interestingly, the formulation BV-7310 showed synergistic activity than any individual extract tested in this assay. BV-7310 also showed potent antioxidant activity in 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. Next, we induced hepatitis in Sprague–Dawley (SD) rats using repeated alcohol (40%) dosing, and carbon tetrachloride (CCl4) 24 hours before termination. Both oral doses of BV-7310 (250 and 500 mg/kg body weight) protected the alcohol-induced body weight loss and significantly improved the elevated levels of liver enzymes compared to the vehicle treated group. Thus, BV-7310 prevents alcohol-induced toxicity in both in-vitro and in-vivo models and could be beneficial for the treatment of ALD or other conditions, which may cause liver toxicity.

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Section: Introductionmentioning

confidence: 99%

Hepatoprotective Activity of BV‐7310, a Proprietary Herbal Formulation of Phyllanthus niruri, Tephrosia purpurea, Boerhavia diffusa, and Andrographis paniculata, in Alcohol‐Induced HepG2 Cells and Alcohol plus a Haloalkane, CCl₄, Induced Liver Damage in Rats

Dey¹,

Chaskar²,

Bhatt³

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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“…Online analytical techniques with universal detectors, such as high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS), can speed up the discovery of new compounds from plants as well as identify those that have previously been reported in the literature [13]. When combined with metabolomic tools, this strategy could enable the fast, accurate evaluation of a massive amount of data, constituting a viable option for the identification of active compounds in plant extracts [14,15].…”

Section: Introductionmentioning

confidence: 99%

Discovery of potential ovicidal natural products using metabolomics

et al. 2019

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Plant extracts are a potential source of new compounds for nematode control and may be an excellent alternative for the control gastrointestinal nematodes that are resistant to conventional anthelmintics. However, research involving natural products is a complex process. The main challenge is the identification of bioactive compounds. Online analytical techniques with universal detectors, such as high-performance liquid chromatography-mass spectrometry (HPLC-MS), together with metabolomics could enable the fast, accurate evaluation of a massive amount of data, constituting a viable option for the identification of active compounds in plant extracts. This study focused on the evaluation of the ovicidal activity of ethanol extracts from 17 plants collected from the Pantanal wetland in the state of Mato Grosso do Sul, Brazil, against eggs of Haemonchus placei using the egg hatchability test. The ethanol extracts were obtained using accelerated solvent extraction. The data on ovicidal activity, mass spectrometry and metabolomics were evaluated using HPLC-DAD-MS, partial least squares regression analysis (PLS-DA) and a correlation map (univariate correlation analyses) to detect compounds that have a positive correlation with biological activity. Among the ten metabolites with the best correlation coefficients, six were phenylpropanoids, two were triterpene saponins, one was a brevipolide, and one was a flavonoid. Combinations of metabolites with high ovicidal action were also identified, such as phenylpropanoids combined with the triterpene saponins and the flavonoid, flavonoids combined with iridoid and phenylpropanoids, and saponins combined with phenylpropanoid. The positive correlation between classes of compounds in plants belonging to different genera and biological activity (as previously identified in the literature) reinforces the robustness of the statistical data and demonstrates the efficacy of this method for the selection of bioactive compounds without the need for isolation and reevaluation. The proposed method also enables the determination of synergism among the classes, which would be impracticable using traditional methods. The present investigation demonstrates that the metabolomic technique was efficient at detecting secondary metabolites with ovicidal activity against H. placei. Thus, the use of metabolomics can be a tool to accelerate and simplify bioprospecting research with plant extracts in veterinary parasitology.

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“…Our group has previously described the use of this workflow to decipher the most active redox compounds in crude extracts of Viola alba subsp. Dehnhardii, Violaceae [15] and to identify antihepatocarcinogenic compounds from plants used to treat liver cancer in Cambodia [16]. Our approach aims to link the chemical profile variability of several extracts or fractions to bioassay results using multivariate data analysis.…”

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confidence: 99%

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

et al. 2019

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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 (IC 50 = 1.96 ± 0.47 µg/mL). Multivariate data analysis of the apolar fractions highlighted a family of triterpenoid compounds, including jacoumaric acid (IC 50 = 1.318 ± 0.59 µg/mL) and corosolic acid (IC 50 = 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.Molecules 2019, 24, 4536 2 of 13 of the human population to the parasite, and human behavior [3]. The disease is characterized by four forms; visceral leishmaniasis, post-kala-azar dermal leishmaniasis, cutaneous leishmaniasis, and mucocutaneous leishmaniasis [4]. Available medical treatments are not sufficient because of their extensive toxicity (e.g., the nephrotoxicity of amphotericin B, the teratogenicity of miltefosine), their lack of efficacy, their expensive cost (amphotericin B), the development of drug resistance (sodium stibogluconate and meglumine antimoniate), and non-specific targeting [4,5]. Fexinidazole, a 5-nitroimidazole, was recently in phase II of clinical trials on visceral leishmaniasis but exhibited a lack of efficacy, and in 2018 no new lead molecules were included in clinical trials [4].Control of leishmaniasis by traditional approaches (vector control and treatment of patients) is facing the difficulties of identifying new cost-effectively produced bioactive molecules able to be produced on an industrial scale, rapid development of drug resistance, and the lack of access to drugs by the threatened populations. These issues are at the heart of concerns of the WHO regarding the control of tropical diseases [6]. Therefore, combination therapies are used to improve the efficacy of antileishmanial therapies and can shorten treatment duration [7]. Furthering our fundamental knowledge through original approaches, herein concerning the activity of natural compounds from a promising plant species active against Leishmania spp., is vital to ov...

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

Cited by 41 publications

References 43 publications

Hepatoprotective Activity of BV‐7310, a Proprietary Herbal Formulation of Phyllanthus niruri, Tephrosia purpurea, Boerhavia diffusa, and Andrographis paniculata, in Alcohol‐Induced HepG2 Cells and Alcohol plus a Haloalkane, CCl₄, Induced Liver Damage in Rats

Hepatoprotective Activity of BV‐7310, a Proprietary Herbal Formulation of Phyllanthus niruri, Tephrosia purpurea, Boerhavia diffusa, and Andrographis paniculata, in Alcohol‐Induced HepG2 Cells and Alcohol plus a Haloalkane, CCl₄, Induced Liver Damage in Rats

Discovery of potential ovicidal natural products using metabolomics

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

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

Cited by 41 publications

References 43 publications

Hepatoprotective Activity of BV‐7310, a Proprietary Herbal Formulation of Phyllanthus niruri, Tephrosia purpurea, Boerhavia diffusa, and Andrographis paniculata, in Alcohol‐Induced HepG2 Cells and Alcohol plus a Haloalkane, CCl4, Induced Liver Damage in Rats

Hepatoprotective Activity of BV‐7310, a Proprietary Herbal Formulation of Phyllanthus niruri, Tephrosia purpurea, Boerhavia diffusa, and Andrographis paniculata, in Alcohol‐Induced HepG2 Cells and Alcohol plus a Haloalkane, CCl4, Induced Liver Damage in Rats

Discovery of potential ovicidal natural products using metabolomics

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

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Product

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Hepatoprotective Activity of BV‐7310, a Proprietary Herbal Formulation of Phyllanthus niruri, Tephrosia purpurea, Boerhavia diffusa, and Andrographis paniculata, in Alcohol‐Induced HepG2 Cells and Alcohol plus a Haloalkane, CCl₄, Induced Liver Damage in Rats

Hepatoprotective Activity of BV‐7310, a Proprietary Herbal Formulation of Phyllanthus niruri, Tephrosia purpurea, Boerhavia diffusa, and Andrographis paniculata, in Alcohol‐Induced HepG2 Cells and Alcohol plus a Haloalkane, CCl₄, Induced Liver Damage in Rats