This review article appraises the extraction methods, compositions, and bioactivities of the essential oils from the Citrus species (family: Rutaceae) endemic to Malaysia including C. aurantifolia, C. grandis, C. hystrix, and C. microcarpa. Generally, the fresh peels and leaves of the Citrus species were extracted using different methods such as steam and water distillation, Likens-Nikerson extraction, solvent extraction, and headspace solid-phase micro-extraction (HS-SPME). Most of the Citrus oils were found to be rich in monoterpene hydrocarbons with limonene (1) as the major component identified in the peels of C. aurantifolia (39.3%), C. grandis (81.6%–96.9%), and C. microcarpa (94.0%), while sabinene (19) was the major component in the peels of C. hystrix (36.4%–48.5%). In addition, citronellal (20) (61.7%–72.5%), linalool (18) (56.5%), and hedycaryol (23) (19.0%) were identified as the major components in the oil of C. hystrix leaves, C. grandis blossom and C. microcarpa leaves, respectively. The C. hystrix essential oil has been experimentally shown to have antimicrobial and antifeedant activities, while no bioactivity study has been reported on the essential oils of other Malaysian Citrus species.

Phaleria macrocarpa (Scheff.) Boerl. is a dense evergreen tree of the family Thymelaeceae. This plant is popular with the name of Mahkota dewa, which is literally translated as God's Crown. All parts of this plant including fruits, seeds, stem, and leaves have well known therapeutic properties and have been extensively used in traditional medicine for the treatment of various diseases such as cancer, diabetes mellitus, allergies, kidney disorders, blood diseases, stroke, and acne with satisfactory results. Scientific findings on bioactivities of P. macrocarpa also demonstrated different pharmacological properties of various parts of this plant including cytotoxic, antidiabetic, antioxidant, anti-inflammatory, antibacterial, and antihypertensive activities. Phytochemicals studies of P. macrocarpa revealed the presence of several classes of compounds such as benzophenones, terpenoids, xanthones, lignans, acids, and sugars. This review aims to provide a critical overview on botanical description, traditional usage, phytochemicals, and pharmacological activities of P. macrocarpa.

Dental caries is a major concern in oral healthcare. Continuous research have been performed extensively in finding new compounds that are capable to solve the problems. Phaleria macrocarpa has been identified effective against hypertension, diabetic, cancer, and diuretic acid. In this study, antiadhesion and antibiofilm activities of Streptococcus mutans were investigated using crude extracts of fruit, leaf and stem of P. macrocarpa. Minimal inhibitory concentration (MIC) assay was conducted to identify the lowest concentration of the extracts required to suppress the activity of S. mutans.  This assay confirmed that all tested extracts were able to inhibit the bacterial activities with concentration of less than 8 mg/mL and thus can be classified as a natural antimicrobial agents.  The extracts were found capable of reducing 50 to 80% of both adhesion and biofilm activity of  S. mutans at 1.56 mg/mL. Results from this study provide a preliminary data for the effectiveness of P. macrocarpa crude extracts as antiadhesion and antibiofilm agent against S. mutans and may have potential for antiseptic agent to treat oral dental caries.

P. macrocarpa is a well known Indonesian medicinal plant which is traditionally claimed to have anticancer properties. To date, there are numerous cytotoxic studies conducted on crude extracts of this plant. However, there are limited informations available regarding cytotoxic activity of the compounds isolated from this plant. Thus, this study investigated cytotoxic activity of two benzophenones derivatives identified as 2,6,4'-trihydroxy-4-methoxybenzophenone (1) and 6,4'-dihydroxy-4-methoxybenzophenone-2-O-β-D-glucopyranoside (2) isolated from the ethyl acetate extract. Cytotoxic activities of these compounds were performed against human cervical carcinoma cell line (HeLa) and mouse embryonic fibroblast cell line (3T3) using MTT assay. The result showed that benzophenone (1)  exhibited low cytotoxic effect against HeLa and 3T3 cell lines with IC50 values of 132 µg/ml and 158 µg/ml, repectively while benzophenone (2) was non toxic against HeLa and 3T3 cell lines are because the IC50 is more than 250 µg/ml. These findings may sheds light on the actual properties of this plant.

Successive extraction method of dried fruits of Phaleria macrocarpa had afforded chloroform, ethyl acetate and ethanol crude extracts. Two benzophenone derivatives which are 2,4,4'-trihydroxy-6-methoxybenzophenone (1) and 4,4'-dihydroxy-2-methoxy-benzophenone-6-O-β-D-glucopyranoside (2) were isolated from the ethyl acetate crude extract. The structures of these compounds were elucidated by spectroscopic techniques using Infrared spectroscopy (IR), 1D (1H, 13C, DEPT), 2D (COSY, HMQC, HMBC) NMR spectroscopy and mass spectrometry. The cytotoxic activity of the crude extracts and benzophenones were tested against human breast carcinoma cell line (MCF-7). MTT assay method was applied to measure the viability of cells at eight different concentrations. The ethyl acetate crude extract was showed higher cytotoxicity activity with IC50 value 126.67 µg/mL compare with ethanol extract (218.33 µg/mL) and chloroform extract (278.33 µg/mL). Meanwhile, benzophenone (1) and benzophenone (2) were exhibited potent cytotoxic properties with IC50 values 141.00 µg/mL and 166.00 µg/mL, respectively.