Chemical profiling and quantification of potential active constituents responsible for the antiplasmodial activity of Cissampelos pareira

Bhatt, Vinod; Kumari, Surekha; Upadhyay, Pooja; Agrawal, Prakhar; Anmol, -; Sahal, Dinkar; Sharma, Upendra

doi:10.1016/j.jep.2020.113185

Cited by 38 publications

(36 citation statements)

References 36 publications

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“…The experiment also revealed an abundance of the best binding drugs which had comparable binding energies to previously reported regulatory molecules. Interestingly, magniflorine, cissamine and hyatinine were recently isolated from the hydro-ethanolic extract of Cipa shown to have antiplasmodial effect (8). These compounds are also present in the aqueous extract and have a competent binding energy with estrogen receptor alpha.…”

Section: Discussionmentioning

confidence: 99%

“…The total alkaloid content in the extract was 46.4 mg/g with cissamine (18.6 mg/g) being the major one, followed by magnoflorine (12.9 mg/g). The quantification of marker compounds in the root sample (USCPR-PE-R) has been reported earlier (8). The marker compounds are also quantified in the water extract (USCP-PE) (supplementary methods, Fig S12).…”

Section: Activity Of Cipa Constituents In In Vitro Inhibition Of Sarsmentioning

confidence: 93%

“…It is also widely used for treating asthma, cough, skin ulcers, snakebite, and jaundice in many parts of the world (6). Alcoholic and aqueous alcoholic extracts of CIPA have antiviral and antimalarial activities, respectively (7,8). However, there is limited research on exploring whether there are shared pathways through which these extracts work in such diverse diseases.…”

Section: Introductionmentioning

confidence: 99%

“…L. (Cipa) a popular herbal medicine, has traditionally been used for fever, contraception and other reproductive system related disorders 4–6 . It is also widely used for treating asthma, cough, skin ulcers, snakebite, and jaundice in many parts of the world 5 .…”

Section: Introductionmentioning

confidence: 99%

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Transcriptome analysis and connectivity mapping ofCissampelos pareiraL. provides molecular links of ESR1 modulation to viral inhibition

Haider

Dholakia

Panwar

et al. 2021

Preprint

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In traditional systems, a single herbal formulation is often used in the treatment of diverse diseases, including some that are newly emergent and prevalent today. We provide here a multi-omics framework to probe the molecular basis of a multicomponent example herb, Cissampelos pareira L. (Cipa) used in the treatment of hormonal disorders and fever in Ayurveda. Cipa treated MCF7 cells exhibit downregulation of signatures of estrogen response. 38 constituent molecules in Cipa potentially bind (∆G< -7.5) with ERα at the same site as estrogen. Cipa transcriptome signatures in the connectivity map exhibit positive scores with protein translation inhibitors and knockdown signatures of genes linked to the antiviral response. This includes the knockdown signature of RPL7, a coactivator of ESRI with a connectivity score > 99.69. This axis was found to be upregulated in the COVID-19 patient transcriptome. The antiviral activity through ESR1 modulation was validated in the DENV-2 infection model. We further observed 98% inhibition of SARs-COV-2 replication in infected Vero cell cultures with the whole extract. A few of its prominent pure constituents e.g pareirarine, cissamine, magnoflorine exhibited 40-80% inhibition. This study provides a novel framework for querying the molecular links of multicomponent Ayurveda formulations and explains their use in the treatment of disparate diseases. The novel biological targets identified here can become potential that could be applicable to more than one viral infection, such as the use of Cipa in dengue and COVID-19.

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Section: Discussionmentioning

confidence: 99%

Section: Activity Of Cipa Constituents In In Vitro Inhibition Of Sarsmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Transcriptome analysis and connectivity mapping ofCissampelos pareiraL. provides molecular links of ESR1 modulation to viral inhibition

Haider

Dholakia

Panwar

et al. 2021

Preprint

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“…The plant has been obtained and isolated as per CSIR, India guidelines (details for extract preparation in supplementary information 1.2). The pure molecules from roots of the plant were isolated as reported recently (8).…”

Section: Methodsmentioning

confidence: 99%

Anti-SARS-CoV-2 potential of Cissampelos pareira L. identified by Connectivity map-based analysis and in vitro studies

Haider

Bhatt

Dholakia

et al. 2021

Preprint

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BackgroundViral infections have a history of abrupt and severe eruptions through the years in the form of pandemics. And yet, definitive therapies or preventive measures are not present.PurposeHerbal medicines have been a source of various antiviral compounds. An accelerated repurposing potential of antiviral herbs can provide usable drugs and identify druggable targets. In this study, we dissect the anti-coronavirus activity of Cissampelos pareira L (Cipa). using an integrative approach.MethodsWe analysed the signature similarities between predicted antiviral agents and Cipa using the connectivity map (https://clue.io/). Next, we tested the anti-SARS-COV-2 activity of Cipa in vitro. A three-way comparative analysis of Cipa transcriptome, COVID-19 BALF transcriptome and CMAP signatures of small compounds was also performed.ResultsSeveral predicted antivirals showed a high positive connectivity score with Cipa such as apcidin, emetine, homoharringtonine etc. We also observed 98% inhibition of SARS-COV-2 replication in infected Vero cell cultures with the whole extract. Some of its prominent pure constituents e.g pareirarine, cissamine, magnoflorine exhibited 40-80% inhibition. Comparison of genes between BALF and Cipa showed an enrichment of biological processes like transcription regulation and response to lipids, to be downregulated in Cipa while being upregulated in COVID-19. CMAP also showed that Triciribine, torin-1 and VU-0365114-2 had positive connectivity with BALF 1 and 2, and negative connectivity with Cipa.

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A conversation between hyphenated spectroscopic techniques and phytometabolites from medicinal plants

Puri

Sahal

Sharma

2021

Analytical Science Advances

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Medicinal plant metabolomics has emerged as a goldmine for the natural product chemists. It provides a pool of bioactive phytoconstituents leading to accelerated novel discoveries and the elucidation of a variety of biosynthetic pathways. Further, it also acts as an innovative tool for herbal medicine's scientific validation and quality assurance. This review highlights different strategies and analytical techniques employed in the practice of metabolomics. Further, it also discusses several other applications and advantages of metabolomics in the area of natural product chemistry. Additional examples of integrating metabolomics with multivariate data analysis techniques for some Indian medicinal plants are also reviewed. Recent technical advances in mass spectrometry-based hyphenated techniques, nuclear magnetic resonance-based techniques, and comprehensive hyphenated technologies for phytometabolite profiling studies have also been reviewed. Mass Spectral Imaging (MSI) has been presented as a highly promising method for high precision in situ spatiotemporal monitoring of phytometabolites. We conclude by introducing GNPS (Global Natural Products Social Molecular Networking) as an emerging platform to make social networks of related molecules, to explore data and to annotate more metabolites, and expand the networks to novel "predictive" metabolites that can be validated.

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Chemical profiling and quantification of potential active constituents responsible for the antiplasmodial activity of Cissampelos pareira

Cited by 38 publications

References 36 publications

Transcriptome analysis and connectivity mapping ofCissampelos pareiraL. provides molecular links of ESR1 modulation to viral inhibition

Transcriptome analysis and connectivity mapping ofCissampelos pareiraL. provides molecular links of ESR1 modulation to viral inhibition

Anti-SARS-CoV-2 potential of Cissampelos pareira L. identified by Connectivity map-based analysis and in vitro studies

A conversation between hyphenated spectroscopic techniques and phytometabolites from medicinal plants

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