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Hypertension remains one of the most significant global health challenges, affecting over 1.3 billion people worldwide and contributing to increased risks of cardiovascular, renal, and cerebrovascular complications (World Health Organization [WHO], 2023). Current synthetic antihypertensive drugs such as angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers, and ?-blockers, though effective, are often associated with adverse effects and limited accessibility in developing countries. Consequently, plant-based antihypertensive research has gained momentum as a safer and more sustainable alternative. Codiaeum variegatum (L.) Blume (Euphorbiaceae), commonly known as garden croton, has been reported for multiple pharmacological effects, including antioxidant, anti-inflammatory, antimicrobial, and cardiovascular activities. Its leaves contain an abundance of flavonoids, phenolics, and terpenoids that are hypothesized to exhibit ACE-inhibitory and vasodilatory actions. This review summarizes the various in vitro methods used to evaluate the antihypertensive potential of C. variegatum leaf extract, focusing on ACE inhibition, renin inhibition, nitric-oxide release, calcium-channel modulation, and antioxidant-linked assays. Analytical techniques, result interpretations, advantages, and limitations of each assay are critically discussed. The review also explores correlations with in vivo and in silico studies, providing insights into mechanistic understanding and methodological standardization. The findings suggest that C. variegatum leaf extract demonstrates potent in vitro ACE inhibition and free-radical scavenging activities, reinforcing its potential as a natural antihypertensive agent.
Hypertension, defined as persistent elevation of arterial blood pressure beyond 140/90 mm Hg, is a multifactorial disorder resulting from genetic, environmental, and metabolic factors (Fuchs et al., 2022). The pathophysiology involves complex interactions between vascular resistance, renal sodium regulation, and neurohormonal control. Among the key modulators is the rennin angiotensin–aldosterone system (RAAS), where the enzyme angiotensin-converting enzyme(ACE) converts angiotensin I to the potent vasoconstrictor angiotensin II, elevating blood pressure and stimulating aldosterone secretion (Bernstein et al., 2018). Therefore, inhibition of ACE has become a central therapeutic strategy. Codiaeum variegatum (L.) Blume, belonging to the Euphorbiaceae family, is an ornamental shrub native to Southeast Asia and widely cultivated in tropical regions (Kumar et al., 2022). The plant is known for its colorful variegated leaves and traditional medicinal uses in treating inflammation, ulcers, and hypertension. Phytochemical investigations have revealed the presence of flavonoids, alkaloids, tannins, phenolic acids, and terpenoids, which contribute to diverse biological activities (Rahman & Ali, 2021). Given the rising global burden of hypertension and limitations of synthetic drugs, evaluating plant-derived bioactive compounds through reproducible in vitro assays is essential. This review aims to systematically present the different in vitro methods employed to assess the antihypertensive activity of C. variegatum leaf extract, emphasizing methodological principles, analytical interpretation, and research prospects.
2. Phytochemical Profile of Codiaeum variegatum
Phytochemical screening of C. variegatum leaves reveals several secondary metabolites including flavonoids (quercetin, rutin), phenolic acids (caffeic, gallic, ferulic acid), terpenoids, tannins, saponins, and alkaloids (Singh et al., 2020). Flavonoids and phenolics act as potent antioxidants and ACE inhibitors due to their ability to chelate metal ions and scavenge free radicals (Lee et al., 2019). Terpenoids and saponins contribute to vasorelaxant and diuretic effects, further supporting antihypertensive potential (Patel et al., 2022).
Table 1. Major phytochemical classes and their antihypertensive mechanisms
Phytochemical class
Representative compounds
Probable mechanism of action
References
Flavonoids
Quercetin, Rutin
ACE inhibition, NO release
Lee et al., 2019
Phenolic acids
Gallic, Caffeic acid
Antioxidant, endothelial protection
Kumar et al., 2022
Terpenoids
Lupeol, β-amyrin
Calcium-channel modulation
Reddy et al., 2017
Saponins
Polygalacin D
Diuretic effect and vasorelaxation
Patel et al., 2022
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