Table 2.

A summary of the pharmacological effects and details of both ANs and ANEs.

Pharmacological Effects	Main Bioactive Phytoconstituents	Main Experimental Methods	Dosage	Main Mechanism of Action	Reference
Antidepressant activity	Ethanol, hexane, ethyl acetate, aqueous extract fractions of the AN	Forced swim test; tail suspension test; locomotion test; Monoamine oxidase assay.	2.5, 5, 10, 13, 20 and 50 mg/kg	The alkaloids viz arecaine, arecaidine, and arecoline have been shown to be present in the AN with only arecoline having MAO-inhibiting properties. The possibility that the MAO inhibition in the present report may be due to arecoline and some other unknown compounds needs further investigation.	[66]
	Dichloromethane and aqueous extract of the AN	Tail-suspension test; yohimbine potentiation test; locomotor test; monoamine oxidase assay.	5 mL/kg and 10 mL/kg for rats and mice	Inhibiting monoamine oxidase type A in rat brain homogenates.	[67]
	Ethanol extracts from AN	Acute and sub-chronic forced swimming tests.	AN ethanol extract (50 mg/kg), aqueous extract (20 mg/kg)	Increased serotonin levels by approximately 35% and norepinephrine levels by approximately 30%.	[69]
	Areca Thirteen Pill (GY-13)	Sucrose preference tests, open field tests, and body weight measurements.	0.25 g/kg (low), 0.50 g/kg (medium), 1.00 g/kg (high)	Increases the levels of cAMP and PKA, restores the mRNA levels of CREB and BDNF, and enhances growth activity in the hippocampus.	[72]
Anti-inflammatory activity	Acetone, ethanol extract of ANs	Paw edema in rats; free radical scavenging activity.	10, 50, and 100 mg/kg	Carrageenan in rats and reduce the levels of prostaglandin E2; the inhibition of cyclooxygenase.	[75]
	Active components of ANs	Quantitative real-time PCR analysis; detection of IL-6 production; apoptosis analysis; cell cycle analysis.	2 mg/kg	Lower the levels of interleukin-6 (IL-6); increase the levels of the tumor suppressor factor p53	[76]
	The water extract derived from the pericarpium of AN	Biochemical analysis; Masson’s trichrome staining Immunofluorescence staining; real-time RT-PCR; Western blot.	50, 100, or 200 mg/kg	Deactivating pancreatic stellate cells; the water extract from ARP exhibited the ability to impede the constituents of the extracellular matrix (ECM), specifically targeting alpha-smooth muscle actin (α-SMA), collagen I, and fibronectin 1 (FN1) in both pancreatic tissue and pancreatic stellate cells (PSCs).	[78]
Anti-inflammatory activity	Gwakhyangjeonggi-san (GHJGS)	LPS-induced phosphorylation of mitogen-activated protein kinases; Western blotting and enzyme-linked immunosorbent assay (ELISA).	0, 250, 500 or 1000 µg/mL	Increased expression of heme oxygenase-1 and prevention of reactive oxygen species generation.	[81]
Anti-inflammatory activity	Arecoline	Bone marrow macrophage (BMM) isolation; cell viability assay; osteoclast differentiation; tartrate-resistant acid phosphatase (TRAP) staining; real-time RT-PCR; Western blot.	10 mg/kg	The interference of arecoline with signal pathways activated by AKT, MAPK, and NF-κB, leading to the suppression of gene expression and the translocation of genes associated with osteoclast differentiation.	[82]
	AN polyphenols	Cell viability assays; specific marker protein detection; fluorescence investigations	0, 25, 50, 100, 150 μg/mL	Areca nut seed polyphenol (ACP) remarkably enhanced the content of ALP in osteoblasts, which promoted the differentiation of osteoblasts.	[84]
Antioxidant activity	AN polyphenol; ethanol extract from AN	Quantitative real-time PCR analysis; Western blot; free radical scavenging activity assays.	Oral administration of ANE (250 mg/kg and 500 mg/kg)	Inhibit vascularization in plasma protein-nitroglycerin venous and local models, as well as inhibit the expression of inducible nitric oxide.	[88]
	AN polyphenol	Quantitative real-time PCR analysis; Western blot; free radical scavenging activity assays.	IC50 values were 26.9 mg/mL for porcine pancreatic elastase and 60.8 mg/mL for human neutrophil elastase.	The elimination of free radicals and the enhancement of antioxidant enzyme activities, such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX).	[89]
	AN polyphenol	Free radical scavenging activity assays.	IC50 = 1483.43 μg DW/mL	Inhibiting elastase, reduction in skin tissue aging and inflammation.	[90]
	EtOAc extract from AN	DPPH radical scavenging assay; hydroxyl radical scavenging activity.	20, 40, 60, 80, 120, and 200 µg/mL	The polyphenols in the ethanol extract of areca nut seed can remove free radicals and exert antioxidant activity.	[94]
Antimicrobial Activity	Methanol, ethanol, and water extract from ANs	Agar disk diffusion assay; microtiter broth dilution method; agar disc diffusion technique.	The agar disc diffusion technique: 100 mg/L	AN is rich in tannins, terpenoids, alkaloids, and flavonoids, and tannin in AN is effective to inhibit gram-positive bacteria. Tannin binds with peptide on the peptidoglycan component from cell walls, which in turn disturb the integrity of bacterial cell walls, which cause bacterial cell damage. Finally, it led to disturbance of the metabolism process and, subsequently, the death of cells.	[98]
	AN polyphenols	Microwave and Soxlet apparatus; resazurin microtiter assay.	MIC: 0.975 ± 0.02 µg/mL	The bioactivity of the extract was attributed to the nontoxic polyphenols present. This extract also showed selective inhibition of M. tuberculosis over other gram-positive and gram-negative bacteria.	[99]
	ANE	High-performance liquid chromatography (HPLC) method; phagocytosis assay; analysis of macrophage activity and capacity; analysis of serum biochemistry.	Oral administration of ANE (500, 1000, or 1500 mg/kg)	Administration of areca nut extract increased the number of WBCs and improved the activity and capacity of macrophages significantly in rats infected with S. aureus.	[102]