Phytochemical Study of Belalai Gajah (Clinacanthus nutans Lindau) as Analgesic Agent Using Pharmacophore Modelling and Biological Assay

Tiara Nales, Nyawai (2021) Phytochemical Study of Belalai Gajah (Clinacanthus nutans Lindau) as Analgesic Agent Using Pharmacophore Modelling and Biological Assay. Masters thesis, Universiti Malaysia Sarawak (UNIMAS).

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Abstract

Pain is a global health problem that impairs life quality. The rapid advancement in drug study is still relying on herbal plants as the source for bioactive compounds. First documented by Nicolaas Laurens Burman in 1984, Belalai gajah (Clinacanthus nutans Lindau) is a herbal plant from Acanthaceae family that is well-known in Asia as a herbal remedy for snake bites, herpes infection, skin infection, cancer, dysentery and diabetes. In recent years, phytochemical screening of C. nutans revealed the presence of bioactive metabolites which potentially contributes to its antiviral, antimicrobial, antioxidant and anti-inflammatory properties as reported in previous studies. However, it is difficult to determine the safe dosage of C. nutans when it is used in different ways. Much of the studies were conducted through in vivo method which provided little information on biomolecular interaction. Therefore, this study aimed to extract, isolate and elucidate compounds from C. nutans. The potential of C. nutans phytochemicals as analgesic was assessed via ligand-based and structure-based pharmacophore modelling. Antioxidant assay, toxicity assay and analgesic assay of extracts, partitions and isolated compounds of C. nutans were conducted in this study. C. nutans leaves was extracted and proceeded to compound isolation using column chromatography technique. Using spectroscopy technique, three compounds were elucidated as 3,7,11,15-tetramethyl-2-hexadecen-1-ol, (2S)-1-O-linolenoyl-3-O-β-D-galactopyranosyl glycerol and 8-β-D-glucopyranosyl-5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one. These compounds were described as EA-1, EA-2 and MEOH-1, respectively. Pharmacophore analysis of isolated and reported compounds were conducted using LigandScout 4.2 software. Pharmacophore model was generated from training set comprised of analgesic drugs. Test set was aligned to pharmacophore model to obtain fit value and common pharmacophore features. Crystal structure of cyclooxygenase-2 (COX-2) with bound ibuprofen was the selected target complex. The interaction of test set to amino acid residue in binding site and score were obtained. 2,2-diphenyl-1-picrylhydrazyl (DPPH) antioxidant, toxicity and in vivo analgesic assay were conducted to evaluate biological activity of extract and isolated compounds. Pharmacophore analysis showed MEOH-1 and EA-2 had good fit value (53.59, 52.85), five interactions with pharmacophore model but EA-1 was scored low (43.64). Isoorientin and isovitexin were scored best with six pharmacophore interactions compared to other test set. MEOH-1 had better alignment score to COX-2 active site than EA-1 and EA-2 with value 45.45, 45.36 and 40.18, respectively. Orientin and isomollupentin scored the best among all test set. MEOH-1 satisfied all Lipinski’s parameter, while EA-2 and EA-1 did not satisfy molecular weight and Log P value. MeOH partition had the best antioxidant activity of IC50 15.73 µg/mL while MEOH-1 was IC50 19.27 µg/mL. C. nutans was concluded to be less toxic (LC50 < 1000 µg/mL) with hexane partition had the highest LC50 value of 128.4 µg/mL. LD50 of extracts and all partitions were determined to be greater than 2000 mg/kg and classified closely to Category 5. Both analgesic tests revealed MeOH extract to have better capability to prolong latency response than partitions but did not show significant analgesic effect as compared to ibuprofen (p<0.05) at concentration 200 mg/kg. To conclude, C. nutans leaves extract had mild analgesic effect, possess bioactive compounds suitable as analgesic agent based on pharmacophore interaction and in vivo assay. C. nutans extracts and partitions are not toxic, and safe for consumption.

Item Type: Thesis (Masters)
Additional Information: Thesis (MSc.) - Universiti Malaysia Sarawak , 2021.
Uncontrolled Keywords: Belalai gajah, Clinacanthus nutans, Nicolaas Laurens Burman, pharmacophore analysis, antioxidant, analgesic agent, spectroscopy technique, chromatographic technique.
Subjects: Q Science > QD Chemistry
Q Science > QK Botany
R Medicine > R Medicine (General)
R Medicine > RM Therapeutics. Pharmacology
Divisions: Academic Faculties, Institutes and Centres > Faculty of Resource Science and Technology
Depositing User: TIARA NALES ANAK NYAWAI
Date Deposited: 24 Feb 2021 04:21
Last Modified: 04 Mar 2021 03:38
URI: http://ir.unimas.my/id/eprint/34504

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