Cissus quadrangularis, also known as veldt grape, adamant creeper, or devil’s backbone, is a plant that belongs to the grape family. Native to certain parts of Asia, Africa and the Arabian Peninsula, Historically, it has been used to treat many conditions, including obesity, hemorrhoids, gout, asthma and allergies and recent research has found that this power-packed plant may also help promote bone health, relieve joint pain and protect against chronic conditions like heart disease, diabetes and stroke 9
(Jia et al., 2014). The healing properties of this plant are attributed to its high contents of vitamin C and antioxidant compounds like carotenoids, tannins and phenols. Traditionally,
Cissus quadrangularis has been shown to reduce obesity in humans but there is no scientific evidence to support these uses. In the present study, biological activity has been proved using a computational approach
(Garrow et al., 2006).
The fundamental goal in drug design is to predict whether a given molecule will bind to a target and if so how strongly
. In-silico docking experimentation involved predictions from biological data with computer-based models to reduce the use of the biological system. This computational tool has the vast range to allow researchers to refine their experimental database reducing costs and time and increasing the research efficacy.
In-silico interaction analysis between therapeutic markers and plant bioactive principles is the modern trend in the drug industry to identify drug-like molecules.
In-silico methods can help in identifying drug targets via bioinformatics tools. Computational tools offer the advantage of delivering new drug candidates more quickly and at a lower cost
(Julius, 2006).
The proteins thyroid-stimulating hormone (TSH), thyroid peroxidase (TPO) and thyroid peroxidase (TPO) and thyroglobulin which are involved in the thyroid signaling pathway were undertaken for the study. The proteins were selected based on the role they play in the thyroidsignaling pathway. The protein TSH, thyroglobulin and thyroid peroxidase have 16, 102 and 23 active sites respectively. These binding sites were predicted using the Biovia Commercial tool. Table 1 shows the selected proteins and the number of active sites present
(Kim, 2015).
The phytochemicals present in the
Cissus quadrangularis have been identified based on documentary evidence. The 3D structure of the phytochemicals has been retrieved from the PubChem database which has been listed in Table 2.
After the identification of receptors of the thyroid signaling pathway and phytochemicals of
Cissus quanragularis, molecular interaction work was undertaken with the help of BIOVIA discovery studio 2020. The results of the interaction study have been depicted here under Table 3 and Plate 1-3.
Pharmacokinetics and pharmacodynamics result
Pharmacokinetic analysis the ADME studies carried out using Swiss ADME revealed the pharmacokinetic properties of ascorbic acid, ampyrone and. The gastrointestinal absorption is high whereas penetration of the blood-brain barrier is absent in both theligands. Skin permeability varies from -6.02 to -7.82 cm/s suggestive of topical application.
Toxicity predictions
Toxicological screening is very important for the development of new drugs and the extension of the therapeutic potential of existing molecules. The US Food and Drug Administration (FDA) states that it is essential to screen new molecules for pharmacological activity and toxicity potential in animals.
Toxicity was predicted with the help of the tool PreADMET. The results showed that the interacting phytochemicals are free from toxicity.
Pharmacodynamic study
The pharmacodynamic study was carried out with PASS online server. The results have been displayed in Plate 4- 7.
Cissus quadrangularis, also known as veldt grape, adamant creeper, or devil’s backbone, is a plant that belongs to the grape family. Native to certain parts of Asia, Africa and the Arabian Peninsula, Historically, it has been used to treat many conditions, including obesity, hemorrhoids, gout, asthma and allergies and recent research has found that this power-packed plant may also help promote bone health, relieve joint pain and protect against chronic conditions like heart disease, diabetes and stroke. The healing properties of this plant are attributed to its high contents of vitamin C and antioxidant compounds like carotenoids, tannins and phenols. Traditionally,
Cissus quadrangularis has been shown to reduce obesity in humans but there is no scientific evidence to support these uses. In the present study, biological activity has been proved using a computational approach
(Lee, 2016).
The fundamental goal in drug design is to predict whether a given molecule will bind to a target and if so how strongly
. In-silico docking experimentation involved predictions from biological data with computer-based models to reduce the use of the biological system. This computational tool has the vast range to allow researchers to refine their experimental data by reducing costs and time and increasing the research efficacy
(Morris, Huey and Olson, 2008).
In-silico interaction analysis between therapeutic markers and plant bioactive principles is the modern trend in the drug industry to identify drug-like molecules.
In-silico methods can help in identifying drug targets
via bioinformatics tools. Computational tools offer the advantage of delivering new drug candidates more quickly and at a lower cost
(Kazemipoor, 2014).
The proteins thyroid-stimulating hormone (TSH), thyroid peroxidase (TPO) and thyroid peroxidase (TPO) and thyroglobulin which are involved in the thyroid pathway were undertaken for the study. The Proteins were selected based on the role they play in the thyroidsignaling pathway
(Mullur, 2014). The protein TSH, thyroglobulin and thyroid peroxidase have 16, 102 and 23 active sites respectively. These binding sites were predicted using the Biovia Commercial tool
(Nagani et al., 2011).
The 3D structure of the 10 phytochemicals present in the
Cissus quadrangularis was screened from the PubChem database. The phytochemicals were subjected to pharmacokinetic and pharmacodynamic studies to identify their efficacy and toxicity
(Prabhavathi et al., 2016).
The ADME studies carried out using PreADMET revealed the pharmacokinetic properties of the interacting 3 phytochemicals. The gastrointestinal absorption is high whereas penetration of the blood-brain barrier is absent in both the ligands. Skin permeability varies from -6.02 to -7.82 cm/s suggestive of topical application.
The pharmacokinetic study showed that the compounds are free from toxicity. The pharmacodynamics activity reveals that the compounds have very good anti-obese activity. The molecular interaction study was carried out with Biovia software and the interaction was measured based on the docking score. Similar studies were performed in
Zhang (2008). Although all the phytochemicals present in
Cissus quandragularis have good interaction with all the proteins involved in the thyroid signaling pathway only the compounds with a score of 60 were taken into consideration. The compounds have very good bindingactivity against the thyroid receptors.
From the study, it is evident that the ascorbic acid had a good interaction with all the three targets with dock scores of 87.93,120.123 and 81.00 respectively and the binding energy is also less. The phytochemical amoyrone has good interaction with TSH and TPO with dock scores of 105.20 and 170.31 respectively (
Kaur and Malik 2014).
Natural remedies have been used for a long time for the treatment of obesity in our traditional healthcare practices. Our study supports the traditional practices.
Future research
A deeper understanding of the interaction of ligands Amoyrone and Ascorbic acid on proteins involved in lipid metabolism through other approaches (
in vivo and
in vitro) might be undertaken to produce novel drug candidates to safeguard mankind from obesity.
