This article aims to review the scientific data on phytochemical and pharmacological studies of Artocarpus collected from Malaysia as well as to highlight their usage as ethnomedicine worldwide. About 55 Artocarpus species are distributed worldwide and 32 of the Artocarpus species can be found in Malaysia. Artocarpus species are well known worldwide for their edible fruits such as Artocarpus heterophyllus (jackfruit), Artocarpus integer (chempedak), and Artocarpus communis (breadfruit). Aside from its edible fruits, the timber is valued for light constructions, crates, large canoes, and boats. The literature for this review was searched using the term ‘Artocarpus’, ‘Artocarpus Malaysia’, ‘Artocarpus extracts’, ‘Artocarpus traditional medicine’ and ‘Artocarpus ethnomedicine’ from published books and scientific journals via various engines such as The Web of Science, PubMed, Science Direct, Scopus, Research Gate, and Google Scholar. The references cited from the retrieved articles were also scanned and cross-checked. All published studies on phytochemical and pharmacological activities of Malaysia’s Artocarpus species up to January 2021 were included in this review. Articles on phytochemical studies of Malaysia’s Artocarpus revealed the isolation of flavonoids as the major constituents. Research on pharmacological activities of the isolated phytochemicals showed that these compounds exhibited significant disease-linked-enzyme (tyrosinase, cholinesterase, glucosidase) inhibitors as well as antioxidant, anti-inflammatory, antimicrobial, and cytotoxic activities. The ethnomedicinal data gathered are useful to understand and prioritize Artocarpus species that can contribute to potent phytochemicals and possibly new drug leads. This review also provides valuable information for the future development of isolated compounds from Artocarpus species.

Objective: To evaluate the anti-inflammatory activity of Crotalaria ferruginea extract (CFE) and its mechanism. Methods: An intratracheal lipopolysaccharide (LPS) instillation-induced acute lung injury (ALI) model was used to study the anti-inflammatory activity of CFE in vivo. The LPS-induced shock model was used to analyze the effect of CFE on survival. LPS-stimulated RAW264.7 cell model was used to investigate the anti-inflammatory activity of CFE in vitro and the effects on mitogen-activated protein kinase (MAPK) or nuclear factor-κB (NF-κB) signaling pathways. Results: CFE administration decreased the number of inflammatory cells, reduced the levels of tumor necrosis factor-α (TNF-a), monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), and interferon-γ, and diminished protein content in the bronchoalveolar lavage fluid of mice. CFE also reduced lung wet-to-dry weight ratio, myeloperoxidase, and lung tissue pathological injury. CFE pre-administration improved the survival rate of mice challenged with a lethal dose of LPS. CFE reduced LPS-activated RAW264.7 cells to produce nitric oxide, TNF-α, MCP-1, and IL-6. Furthermore, CFE inhibited nuclear translocation and phosphorylation of NF-κB P65, extracellular signal-regulated kinase, c-Jun N-terminal kinases, and P38 MAPKs. Conclusions: CFE exhibits potent anti-inflammatory activity in LPS-induced ALI mice, LPS-shock mice, and RAW264.7 cells, and its mechanism may be associated with the inhibition of NF-κB and MAPK signaling pathways. Crotalaria ferruginea may be a useful therapeutic drug for the treatment of ALI and other respiratory inflammations.

Objective: To explore the anti-inflammatory and antipyretic effects of methanolic leaf extract from Arbutus andrachne and its mechanism of action. Methods: Paw edema was induced by intraplantar (i.pl.) injection of λ-carrageenan (1% w/v, 100 μL/paw) while pyrexia was evoked by intraperitoneal (i.p.) injection of 20% baker’s yeast (20 mL/kg body wt) in male Wistar rats. The anti-inflammatory and antipyretic effects of Arbutus andrachne methanolic leaf extract were explored by injecting rats with different doses of the plant extract (150, 300, and 600 mg/kg body wt, i.p.). Selective antagonists for transient receptor potential vanilloid-1 (TRPV1), cannabinoid receptor 1 (CB1), and alpha-2 adrenergic receptor (a2-AR) were used to unravel the extracts’ mechanism of action. Blood samples were collected from the heart of rats to measure the levels of interleukin-6 (IL-6) and prostaglandin E₂ (PGE₂) by enzyme-linked immunosorbent assay. Results: The extract exhibited potent anti-inflammatory activity by decreasing paw thickness and IL-6 levels. In addition, yeast-evoked pyrexia was attenuated by the extract treatment via TRPV1 and CB1 receptors and a reduction in PGE₂ levels. No significant effects were found for a2-AR. Moreover, the rats that received the plant extract demonstrated similar responses to the positive control group. Conclusions: Arbutus andrachne can be a good candidate for treating inflammation and pyrexia and should be further investigated.

Objective: To investigate the antifibrotic effects of Chrysanthemum indicum ethanol extract (CIEE) against activated hepatic stellate cells (HSC) and thioacetamide (TAA)-induced hepatofibrosis in rats. Methods: Cell viability and proliferation of HSC-T6 cells were measured using MTT assay. Primary HSCs were used to study morphology. TAA (200 mg/kg) was used to induced hepatic fibrosis in rats. CIEE (100 and 500 mg/kg) and silymarin (50 mg/kg) were administered orally. Liver functions including alanine transaminase, aspartate transaminase, glutathione, and hydroxyproline levels were measured using commercial kits. Liver sections and fibrotic biomarker expression were measured using hematoxylin and eosin staining and real-time polymerase chain reaction. Results: In vitro study revealed that CIEE (0.1, 0.25, and 0.5 mg/mL) inhibited the proliferation of activated HSCs exposed to transforming growth factor (TGF)-β and restored the activated primary HSC morphology. In in vivo studies, TAA-induced increase in liver/body weight ratio (5.46 ± 0.26) was significantly reduced (4.13 ± 0.22) by CIEE (P<0.05 at 500 mg/kg). CIEE (100 and 500 mg/kg) improved the liver functions by significantly attenuating changes in alanine transaminase, aspartate transaminase, glutathione, and hydroxyproline levels (P<0.05). Further, CIEE (100 and 500 mg/kg) ameliorated the histological changes in liver tissue and TGF-β expression significantly (P<0.05) in TAA-induced rats. Conclusions: CIEE significantly protects against TAA-induced liver damage in rats and can be used in the treatment of liver fibrosis.

Objective: To characterize a nanoemulsion containing a synergistic combination of curcumin (CUR) and quercetin (QUE) for brain targeting through the nose. Methods: The synergistic activity of the combination of two phytoconstituents, curcumin and quercetin (CUR-QUE) was determined at a 2:1 ratio. Nanoemulsions containing the synergistic combination were prepared using high-pressure homogenization technique. Nanoemulsion formulation was characterized for globule size, drug content, thermodynamic stability, zeta potential measurement, and drug release. Histological studies were performed using isolated nasal mucosa of sheep. Moreover, in vivo studies using allograft model were performed. Results: CUR-QUE in a 2:1 ratio combination showed the lowest combination index values 0.99 (combination index<1) for treatment of human glioblastoma U373-MG cell. The combination inhibited the growth of human glioblastoma U373MG cells. The significant drug targeting efficiency percentage (178.25±2.86 for CUR and 170.54±6.11 for QUE) and nose to brain drug direct transport percentage (44.05±0.93 for CUR and 38.25±0.83 for QUE) of optimized nanoemulsion (F9) indicated effective central nervous system targeting via the intranasal route. In vivo anticancer study using allograft model of nude mice demonstrated potential anticancer activity of the synergistic combination of CUR-QUE as compared to doxorubicin. Conclusions: This study demonstrates that synergistic combination of CUR-QUE was optimal for treatment of human glioblastoma. Moreover, significant site-specific delivery to the brain was achieved by administering nanoemulsion through the nose. The study also reveals that intranasal delivery of nanoemulsion containing synergistic combination of CUR and QUE could be a promising strategy for brain tumor treatment.