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Two-dimensional correlation infrared spectroscopy applied to analyzing and identifying the extracts of Baeckea frutescens medicinal materials

Adib AM, Jamaludin F, Kiong LS, Hashim N, Abdullah Z

J Pharm Biomed Anal, 2014 Aug 5;96:104-10.
PMID: 24727283 DOI: 10.1016/j.jpba.2014.03.022

Baeckea frutescens or locally known as Cucur atap is used as antibacterial, antidysentery, antipyretic and diuretic agent. In Malaysia and Indonesia, they are used as an ingredient of the traditional medicine given to mothers during confinement. A three-steps infra-red (IR) macro-fingerprinting method combining conventional IR spectra, and the secondary derivative spectra with two dimensional infrared correlation spectroscopy (2D-IR) have been proved to be effective methods to examine a complicated mixture such as herbal medicines. This study investigated the feasibility of employing multi-steps IR spectroscopy in order to study the main constituents of B. frutescens and its different extracts (extracted by chloroform, ethyl acetate, methanol and aqueous in turn). The findings indicated that FT-IR and 2D-IR can provide many holistic variation rules of chemical constituents. The structural information of the samples indicated that B. frutescens and its extracts contain a large amount of flavonoids, since some characteristic absorption peaks of flavonoids, such as ∼1600cm(-1), ∼1500cm(-1), ∼1450cm(-1), and ∼1270cm(-1) can be observed. The macroscopical fingerprint characters of FT-IR and 2D-IR spectra can not only provide the information of main chemical constituents in medicinal materials and their different extracts, but also compare the components differences among the similar samples. In conclusion, the multi-steps IR macro-fingerprint method is rapid, effective, visual and accurate for pharmaceutical research.
Fulltext Mechanism(s) of action involved in the gastroprotective activity of Muntingia calabura

Zakaria ZA, Balan T, Suppaiah V, Ahmad S, Jamaludin F

J Ethnopharmacol, 2014 Feb 12;151(3):1184-1193.
PMID: 24380736 DOI: 10.1016/j.jep.2013.12.045

ETHNOPHARMACOLOGICAL RELEVANCE: Muntingia calabura L. (Muntingiaceae) is locally known as kerukup siam. Its leaves, flowers, barks and roots have been used traditionally in East Asia and South America to treat various diseases including ulcer-related diseases. The present study aimed to investigate the mechanism(s) of gastroprotective effect of methanol extract of Muntingia calabura leaves (MEMC) using the pylorus ligation induced gastric ulceration in rats.
MATERIALS AND METHODS: Five groups of rats (n=6) were administered orally once daily for 7 days with 8% Tween 80 (negative control), 100 mg/kg ranitidine (positive control), or MEMC (100, 250 or 500 mg/kg), followed by the ulcer induction via ligation of the pyloric part of the rat's stomach. This was followed by the macroscopic analysis of the stomach, evaluation of gastric content parameters, and quantification of mucus content. The antioxidant (measured using the superoxide anion and 2,2-diphenyl-1-picrylhydrazyl (DPPH)-radical scavenging, oxygen radical absorbance capacity (ORAC) and total phenolic content (TPC) assays), anti-inflammatory (evaluated using the in vitro lipoxygenase and xanthine oxidase assays), phytoconstituents and HPLC analysis of MEMC were also carried out.
RESULTS: The MEMC significantly (p<0.05) reduced gastric lesion in this model. Furthermore, the extract also significantly (p<0.01) reduced the volume of gastric content whereas the total acidity was significantly (p<0.05) reduced in the doses of 100 and 500 mg/kg MEMC. Moreover, the mucus content increased significantly (p<0.01) in MEMC-treated rats. The extract also showed high antioxidant and anti-inflammatory activities in all assays tested, and demonstrated the presence of high tannins and saponins followed by flavonoids.
CONCLUSION: The MEMC exerted gastroprotective effect via several mechanisms including the anti-secretory, antioxidant and anti-inflammatory activities. These activities could be attributed to the presence of tannins, saponins and flavonoids (e.g. rutin, quercitrin, fisetin and dihydroquercetin).
Fulltext Hits-to-Lead Optimization of the Natural Compound 2,4,6-Trihydroxy-3-geranyl-acetophenone (tHGA) as a Potent LOX Inhibitor: Synthesis, Structure-Activity Relationship (SAR) Study, and Computational Assignment

Ng CH, Rullah K, Abas F, Lam KW, Ismail IS, Jamaludin F, et al.

Molecules, 2018 Sep 30;23(10).
PMID: 30274341 DOI: 10.3390/molecules23102509

A new series of 2,4,6-trihydroxy-3-geranyl-acetophenone (tHGA) analogues were synthesized and evaluated for their lipoxygenase (LOX) inhibitory activity. Prenylated analogues 4a⁻g (half maximal inhibitory concentration (IC50) values ranging from 35 μ M to 95 μ M) did not exhibit better inhibitory activity than tHGA (3a) (IC50 value: 23.6 μ M) due to the reduction in hydrophobic interaction when the alkyl chain length was reduced. One geranylated analogue, 3d, with an IC50 value of 15.3 μ M, exhibited better LOX inhibitory activity when compared to tHGA (3a), which was in agreement with our previous findings. Kinetics study showed that the most active analogue (3e) and tHGA (3a) acted as competitive inhibitors. The combination of in silico approaches of molecular docking and molecular dynamic simulation revealed that the lipophilic nature of these analogues further enhanced the LOX inhibitory activity. Based on absorption, distribution, metabolism, excretion, and toxicity (ADMET) and toxicity prediction by komputer assisted technology (TOPKAT) analyses, all geranylated analogues (3a⁻g) showed no hepatotoxicity effect and were biodegradable, which indicated that they could be potentially safe drugs for treating inflammation.
Fulltext Synthesis and docking studies of 2,4,6-trihydroxy-3-geranylacetophenone analogs as potential lipoxygenase inhibitor

Ng CH, Rullah K, Aluwi MF, Abas F, Lam KW, Ismail IS, et al.

Molecules, 2014;19(8):11645-59.
PMID: 25100256 DOI: 10.3390/molecules190811645

The natural product molecule 2,4,6-trihydroxy-3-geranyl-acetophenone (tHGA) isolated from the medicinal plant Melicope ptelefolia was shown to exhibit potent lipoxygenase (LOX) inhibitory activity. It is known that LOX plays an important role in inflammatory response as it catalyzes the oxidation of unsaturated fatty acids, such as linoleic acid to form hydroperoxides. The search for selective LOX inhibitors may provide new therapeutic approach for inflammatory diseases. Herein, we report the synthesis of tHGA analogs using simple Friedel-Craft acylation and alkylation reactions with the aim of obtaining a better insight into the structure-activity relationships of the compounds. All the synthesized analogs showed potent soybean 15-LOX inhibitory activity in a dose-dependent manner (IC50 = 10.31-27.61 μM) where compound 3e was two-fold more active than tHGA. Molecular docking was then applied to reveal the important binding interactions of compound 3e in soybean 15-LOX binding site. The findings suggest that the presence of longer acyl bearing aliphatic chain (5Cs) and aromatic groups could significantly affect the enzymatic activity.