A review of the phytochemical compounds and pharmacological activities from selected Ficus plants

The Ficus genus belongs to the Moraceae family were used for medicinal purposes. Distributed in America, Asia, Africa, and Australia, there were sixteen species accepted in Indonesia. They were Ficus callosa, Ficus melinocarpa, Ficus elastica, Ficus drupaceae, Ficus geocarpa, Ficus Superba, Ficus heteropoda, Ficus istulosa, Ficus hirta, Ficus ampelas, Ficus adenosperma, Ficus ardisioides, Ficus consociate, Ficus ribes, Ficus lyrata, Ficus virens Aiton. This article reviewed the scienti icwork of the Ficus genus. Their traditional usage, phytochemical compounds, and pharmacological activity were summarized. This study aims at providing a collection of publications on selected species of Ficus genus. A critical review of the literature data revealed secondary metabolite like triterpenoid, steroid, saponin, lavonoid, phenolic compound and alkaloidwere found in some species of Ficus. Some pure compounds such asquercetin, quercetin3-O-α-L-arabinopyranoside, epilupeol acetate, oleanolic acid, friedelin, elastiquinone, pinocembrin-7-O-β-D-glucoside, and icusoside Bwere isolated. Awide range of pharmacological activitieswas observed. Antimicrobial, antioxidant, antiviral, antiparasitic, cytotoxic, and antimalarial were found in previous researches. Ficus genuswas potential to be developed as a medicinal plant.


INTRODUCTION
Family Moraceae consists of over 50 genera and nearly 1400 species distributed in the tropical and subtropical region as American, Asia, Afrika, and Australia (Zerega et al., 2005). Ficus is one large family plant comprises of over 800 species (Herre et al., 2008) and one of about 40 genera of mulberry family Moraceae (Hamed, 2011). Twenty-two species were recorded in Indonesian, among which 16 are accepted name and six synonyms, which are all deciduous plants, and most are essentially hemiepiphytic. Ficus plant species can be edible food and traditional medicine to improve the human health of about ten thousand years. Several species used were recorded in Ayurvedic and traditional Chinese medicine (Lansky et al., 2008) (Shi et al., 2011).  (Nisar et al., 2014).

F. virens
jangli pipit leaves, fruit and bark Diabetes, ulcer, menstrual disorder, leucorrhea (Khan et al., 2011)    tional medicine for many countries. Thailand people used fresh young leaves of leab (F. Superba) and phak huead Daeng (F. virens) as a vegetable as a curry or used in a salad (Chantarasuwan and Welzen, 2012). The Ayurveda book recorded that traditional people use bark, latex, leaves and fruit of F. virens Aiton for vertigo, blood diseases, diabetes, rheumatism and antioxidant (Rajani et al., 2008). People in Vanuatu used latex from leaves of F. adenosperma for menorrhagia; this plant is added to the coconut water (Bourdy and Walter, 1992). Different from people in Papua New Guinea, used for sores and scabies, but fresh roots of F. adenosperma is chewed to treat malaria (Mahyar et al., 1991). In Vietnam, leaves of F. drupaceae is taken to treat malaria, paragonimiasis, nasosinusitis, sinusitis, and anasarca (Phan et al., 2013). Still, the leaves, roots and bark from F. microcarpa were applied to reduce fever and anti-in lammatory. The usage of Ficus species in Pakistan for traditional medicine can be seen in Table 1.
Butyrospermol cinnamate and isolation of lutein from leaves of F. ampelas were also exposed (Ragasa et al., 2014).

Pharmacological activities
Pharmacological activities of some Ficus species were shown in the explanation below:

Antioxidant Activity
Ethanol extract of young leaves of F. virens Aiton and Ficus callosa had antioxidant activity with DPPH and ABTS assays, which IC 50 of DPPH F. virens Aiton was 0.34 mg/ml, and IC 50 of ABTS 0.23 mg/ml. It was different with F. callosa, IC 50 of DPPH 0.95 mg/ml, and ABTS 0.35 mg/ml. F. virens Aiton had higher lavonoid and phenolic compounds, which correlated with its antioxidant activity (Shi et al., 2011).
Quercetin from methanol leaves extract of F. virens Aiton was the most active DPPH radical scavenging activity with IC 50 14 ± 1.12 µg/ml (Orabi and Orabi, 2016). (Hil i, 2019), reported that ethanol extract of F. elastic gave antioxidant activity with EC 50 DPPH 6.4166 mg/ml and 0.0768 mg/ml with ABTS. Ficuselastic acid and (1'S,6'R)-8-O-β-D-glucopyranosyl abscisate sodium showed antioxidant activity (Kiem et al., 2012). The methanol extract of leaves of Ficus istulosa presented IC 50 DPPH 16.66 µg/ml (Raka et al., 2019). Some Ficus from other country had antioxidant compounds, such as C-glycosyl lavone from ethanolic leaves extract of F. microcarpa , and aqueous roots extracts of F. beecheyana (Yen et al., 2018). Philippines peoples used antioxidants from the ethanol extract of leaves and fruits of F. nota (Santiago et al., 2017). F. sur is a traditional medicine from Togo, had antioxidant activity for the whole plant, the highest activity was given by ethanolic bark extract (56.50 ± 0.29 µg QE/mg), and the ripe fruit had lowest activity (7.3 ± 0.30 µg QE/mg) (Saloufou et al., 2018). The old leaves of F. deltoidea had more potent antioxidant activity than the fresh leaves (Manurung et al., 2017). The value of IC 50 from other extracts of Ficus species are reported in Table 2.

Antimicrobial Activity
The antimicrobial activity of Ficus species has been evaluated by the agar diffusion method. It can be proposed that lavonoids, triterpenoid, and steroid had antimicrobial activities (Wibowo et al., 2018a). Ficus species showed antimicrobial activity against at least one bacteria, which can be seen in Table 3.

Antiviral Activity
Antiviral activity in vitro of lavonoids, which was found from F. virens Aiton on Coxsackie B4 (CVB4), and hepatitis A virus (HAV) were also carried out. Antiviral activities were also given by quercetin and quercetin-3-O-β-D-galactopyranoside isolated from F. virens Aiton.

Cytotoxic Activity
Flavonoid compounds are the secondary metabolites responsible for pharmacological activity in Ficus species. The lavonoid from F. virens Aiton showed low cytotoxic activity in Vero cells by the MTT method (Orabi and Orabi, 2016). The ethanol leaves extract of F. istulosa had cytotoxicity concentration (CC 50 ) >200 µg/ml, which was not toxic, while butanol and chloroform fractions gave CC 50 >100 µg/ml (Ha id et al., 2016). The methanol extract of F. septica root inhibited nasopharyngeal carcinoma (HONE-1) and gastric adenocarcinoma (NUGC) cell (Damu et al., 2009) while the ethanolic extract of roots from F. beecheyana inhibited HL-60 cell (Yen et al., 2018).
Ficusamide is an isolated compound from F. elastica that had medium cytotoxic activity on A-549 lung cancer (Mbosso et al., 2012). Other compounds from F. elastica showed weak cytotoxic activity (IC 50 values 20 µg/ml) on HeLa cell (Teinkela et al., 2018). Meanwhile, compounds from F. drupacea stem barks demonstrated the highest antiproliferative activities against most cancer cells, are reported in Table 4 (Yessoufou et al., 2015).

Other Pharmacological Activities
Methanol fruit extract of Ficus carica with a concentration of 924 µmol/l reduced 54% the formation of uric acid in mice, which injected with potassium oxonate (Mohamed and Al-Okbi, 2008). F. carica leaves showed oedema inhibitory activity (antiin lammatory) in rats induced by carrageenan as much as 48.8% (Ali et al., 2012). Previous research demonstrated that ethanolic fruit extract of F. carica could inhibit α-glucosidase, α-amylase, and pancreatic lipase (Mopuri and Islam, 2016).

CONCLUSIONS
We summarized the traditional usage, phytochemical compounds, and pharmacological activity of selected Ficus plants. Based on the literature review was reported that most of the species were used as a traditional medicine in Asian countries such as Indonesia, Papua New Guinea, Vietnam, Pakistan, Thailand, and Vanuatu. Some species of the Ficus genus need further research on pharmacological activities, based on mechanisms and chemical contents.