A Review on Phytochemistry and Pharmacological Potential of Sonneratia apetala (Keora): A Mangrove Plant of the Sundarbans

A Review on Phytochemistry and Pharmacological Potential of Sonneratia apetala (Keora): A Mangrove Plant of the Sundarbans

¹Shamima Sultana, ¹Mirza Alimullah, ²Md. Ahnaf Tazim, ¹Hridoy Chandra Ghosh, ²Fatiha Fauzia, ¹Tahasin Akhter, ¹Onika Zaman, ¹Md Tayeb Hossen, ¹Nusrat Subhan, ^1*Md. Ashraful Alam

Abstract

Sonneratia apetala (Keora) is a mangrove plant traditionally used for medicinal purposes and increasingly recognized for its pharmacological potential. This review summarizes current knowledge on its phytochemistry and biological activities, with emphasis on antioxidant, antidiabetic, reno-protective, and hepatoprotective effects. Phytochemical studies have identified phenolics, flavonoids, and triterpenoids, including gallic acid, catechin, quercetin, and lupeol, which are closely associated with its bioactivity. Pharmacological investigations demonstrate enzyme inhibition, restoration of antioxidant defenses, modulation of inflammatory mediators, and regulation of metabolic pathways, suggesting broad therapeutic relevance. While these findings are promising, most evidence arises from in vitro and animal models, with limited data on toxicity, bioavailability, and clinical efficacy. Future research should prioritize standardized extract preparation, functional studies, and clinical validation, as well as explore its potential cardioprotective role given its strong antioxidant profile. Collectively, S. apetala represents a valuable natural resource with potential application in nutraceutical and phytopharmaceutical development.

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Current Issue

Volume 3 - Issue 1

Keywords

Mangrove

Keora

Oxidative stress

Antioxidant

Renoprotective

1. Introduction

Since ancient times, medicinal plants have been used as an easily available form of healthcare across different cultures and in recent years they have gained a renewed scientific interest [1]. Secondary metabolites such as flavonoids, polyphenols, alkaloids, terpenoids and tannins, present in abundance within plants offer a wide range of bioactivities which can support disease prevention and therapy [2]. Plant-derived compounds unlike synthetic agents often acts on multiple biological systems which makes them valuable in managing complex, oxidative stress derived conditions like diabetes, liver injury and kidney dysfunction [3]. The mangrove species hold a special place among these plants as they have evolutionarily adapted to survive under the harsh saline, tidal and oxygen poor conditions forcing them to produce unique metabolites with strong defensive properties [4]. Sonneratia apetala Buch.-Ham., or Keora, belonging to the Lythraceae family, is one of the well-known mangrove trees of the Sundarbans and other coastal regions of South and Southeast Asia [5]. Local communities have been using different parts of the plant including its fruits, seeds, pneumatophores, bark and leaves for the management of various ailments [6]. Over the last decade, phytochemical studies have revealed the richness of Keora in bioactive constituents such as gallic acid, catechins, tannins, Vitamin C and fatty acids. These compounds contribute to the antioxidant, anti-inflammatory and metabolic regulating effects of Keora [7]. Theoretically, they can neutralize free radicals, chelate pro-oxidant metals and enhance endogenous antioxidant enzymes, ultimately reducing the oxidative stress and the following damage it would have caused. These biochemical foundations help explain the wide range of pharmacological profiles observed experimentally from Sonneratia apetala ranging from hypoglycemic and hepatoprotective activities to nephroprotective and cardiometabolic effects.

Between the years 2015 and 2025, a growing number of in vitro and in vivo studies have validated many of these traditional claims. Keora extracts have been shown to inhibit carbohydrate processing enzymes, lower blood glucose in diabetic models, exhibit hepatoprotective effects and restore renal antioxidant defenses. Even though the evidence base is still emerging, the preliminary findings highlight Keora as a plant worth further pharmacological and clinical investigations.

This review takes a closer look at Sonneratia apetala and its pharmacological potential especially its antioxidant, antidiabetic, hepatoprotective and reno-protective. It also considers the underlying mechanisms of actions and identifies areas where additional research is required.

2. Methodology

To locate the details on phytochemistry and pharmacological activities of Sonneratia apetala, the literature works were comprehensively searched for relevant studies. The search strategy involved searching keywords, namely, Sonneratia apetala”, “Keora”, “mangrove medicinal plant,” “antioxidant activity,” “antidiabetic,” “hepatoprotective,” and “reno-protective,” from PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar.

After reviewing in vitro, in vivo, and pharmacological research articles for the past decade, full-text articles containing information on S. apetala's phytochemical ingredients, in vitro tests, in vivo models, or mechanism perspectives were obtained only if relevant. The criteria for exclusion included papers with inadequate mechanisms, unrelated mangrove species, or solely ecological studies lacking sufficient pharmacological data. Hence, this review seeks to collect phytochemical and pharmacological information on Sonneratia apetala, presenting an overview of its therapeutic potential and insights for future clinical research.

3. Sonneratia apetala: Mangrove Apple

Sonneratia apetala, with a family of Lythraceae is a mangrove plant that is expanding rapidly and widely found in the tropical coastal regions, especially in the Sundarbans Forest of Bangladesh, India, Malaysia, Australia, China, Myanmar, New Guinea, and other countries [6, 8-10]. It is known by several names in different countries such as Mangrove Apple, Motitavar, Keora, Kandal, Chipi, and Keruan [10]. The fruits of this species are frequently used as food, nutrition, and medicine to treat a variety of ailments [11]. The plant showed antibacterial, cytotoxic, antiviral, antioxidant, and antidiabetic activity[8, 12]. There are many active compounds in the fruit of the plant.

4. Taxonomic Classification of S. apetala

Kingdom: Plantae; Subkingdom: Viridiplantae; Infrakingdom: Streptophyta; Phylum (Division): Tracheophyta; Subphylum (subdivision): Spermatophytina; Class: Magnoliopsida; Superorder: Rosanae; Order: Myrtales; Family: Lythraceae; Genus: Sonneretia; Species: Sonneretia apetala [10] [13]

5. Phytochemistry of S. apetala

The ability of Keora to survive and thrive in harsh, high salinity environment of mangrove forests is directly attributed to its unique and abundant profile of defensive secondary metabolites. These compounds are synthesized by the plants to combat and counteract the severe osmotic and oxidative stress given to it by its habitat [4]. Chemical screening across various plant parts consistently revealed the presence of major classes of bioactive compounds, primarily polyphenols and flavonoids, alongside significant quantities of triterpenoids, alkaloids, and tannins. The high concentration of these metabolites is the pharmacological basis for all the biological activities discussed in this review.

Key compounds identified through isolation and analysis include the potent polyphenols gallic acid and ellagic acid, the triterpenoids lupeol and betulinic acid, and the flavonoids quercetin and catechin. Notably, seeds and fruit pericarp are typically reported as being especially rich in polyphenols and flavonoids. A detailed, compound-by-compound breakdown of the phytochemicals isolated from S. apetala, along with their specific plant source and corresponding literature references, is presented in Tables 1 and 2.

Table 1: Chemical Constituents of the fruit of S. apetala

Group	Compounds	Activity	Structure	Ref.
Phenolic compounds	Caffeic acid	Antioxidant, anti-inflammatory, anticarcinogenic.		[14, 15]
	Syringic acid	Antioxidant, anti-inflammatory, antiproliferative, anticancer, antimicrobial, antiendotoxic.		[14, 16]
	Ferulic acid	Antioxidants, anti-inflammatory, anticarcinogenic, hepatoprotective, and antibacterial.		[14, 17]
	p-Coumaric acid	Antioxidant, anti-bacterial, antitumor, anti-inflammatory.		[14, 18]
	Gallic acid	Antioxidant, anti-inflammatory, antineoplastic.		[14, 19]
	Sinapic acid	Antioxidant, antimicrobial, anti-inflammatory, anticancer.		[14, 20]
	Coumarin	Anticoagulant, antioxidant, anti-inflammatory, antitumor, antiviral, antibacterial.		[14, 21]
	trans-Cinnamic acid	Antioxidant, antibacterial, anti-inflammatory, antitumor.		[7, 22]
	Phenol, 3,5-bis(1,1-dimethylethyl)	Anticancer, antioxidant, antimicrobial.		[7, 23]
	Benzenepropanoic acid	Antioxidant, anti-inflammatory.		[14]
Flavonoids	Quercetin	Anticancer, antioxidant, anti-inflammatory, anti-cardiovascular, anti-aging, neuroprotective.		[14, 24]
	Catechin	Anticancer, antioxidant, anti-inflammatory.		[14, 25]
	Rutin	Antioxidant, anti-inflammatory, anti-proliferative.		[14, 26]
	Myricetin	Antioxidant, anticancer, antidiabetic and anti-inflammatory.		[14, 27]
	Apigenin	Antiproliferative, anti-inflammatory, and antimetastatic		[14, 28]
	Kaempferol	Antioxidant, anti-inflammatory, anticancer, antidiabetic, cardioprotective, neuroprotective.		[7, 29]
Triterpenoids	Lupeol	Anti-inflammatory, antiprotozoal, hepatoprotective, cancer preventive.		[14, 30]
	β-amyrin	Antioxidant.		[14, 31]
Others	1,2-benzene dicarboxylic acid ester	Anticancer, antibacterial, antidiabetic.		[7]
	2-methyltetracosane	Antibacterial, antioxidant.		[7, 32]
	Tetratetracontane	Antioxidant, cytoprotective, hypoglycemic, hypolipidemic, antibacterial.		[7, 33]
	Heptacosane	Antibacterial, antifungal.		[7]
	2-hexyl-1-octanol	Antimicrobial.		[7]
Vitamin	Ascorbic acid	Antioxidant, anti-inflammatory.		[14]
	Vitamin B2	Antioxidant,		[14]
	Vitamin B5	Antioxidant, anti-inflammatory.		[14, 34]
	Vitamin B6	Anti-inflammatory.		[14, 35]

Table 2: Chemical constituents of the seed of S. apetala

Group	Compounds	Activity	Structure	Ref.
Polyphenols	Caffeic acid	Antioxidant, anti-inflammatory, anticarcinogenic.		[6, 15]
	(+)-catechin	Anticancer, antioxidant, anti-inflammatory, and anti-allergy.		[6, 25]
	(-)-epicatechin	Antioxidant, anti-inflammatory, antimicrobial, antitumor, cardioprotective.		[6, 36]
	Ellagic acid	Antioxidant, and antiadipogenic, anticancer.		[6, 37]
	Gallic acid	Antioxidant, anti-inflammatory, antineoplastic.		[6, 19]
	Quercetin	Anticancer, antioxidant, anti-inflammatory, cardioprotective, anti-aging, and neuroprotective.		[6, 19]
	Rutin hydrate	Antioxidant, anti-inflammatory, anti-proliferative.		[26, 38]
	trans-ferulic acid	Antioxidant		[38]
	trans-cinnamic acid	Antioxidant, antibacterial, anti-inflammatory, antitumor.		[22, 38]
	Myricetin	Antioxidant, anticancer, antidiabetic, and anti-inflammatory.		[38]
	Kaempferol	Antioxidant, anti-inflammatory, anticancer, antidiabetic, cardioprotective, neuroprotective.		[30, 38]
Fatty Acids	Margaric acid	Antitumor, antimicrobial.		[39, 40]
	8,11-otadecadienoic acid, methyl ester	Antimicrobial .		[40, 41]
	Steric acid, methyl ester	Antibacterial and antifungal.		[40, 42]
	Linoleic acid, methyl ester	Antioxidant.		[43]
	Oleic acid, methyl ester	Acaricidal, antimicrobial.		[43, 44]
	Oleic acid	Antifungal, antitumor.		[45]
	Arachidic acid	Anti-inflammatory, cardioprotective, anticlotting.		[40, 60]
	Linoleic acid	Anti-inflammatory, anticoagulant, cardioprotective.		[40, 47]
	Stearic acid	Neuroprotective, antioxidant, antilipidemic.		[40, 48]
	Tetracosanoic acid	Antioxidant, anticancer, antihypertensive, anti-inflammatory		[40, 49]
	Palmitic acid	Antioxidant, anticancer, antihypertensive, anti-infalmmatory		[12]
Ester	bis(2-ethylhexyl) ester	Antimutagenic.		[38, 50]
Ester	1,3-benzenedicarboxylic acid	Catalyst.		[38]
Triterpenoid	Lupeol	Anti-inflammatory, anticancer, antimicrobial.		[10]
	β-amyrin	Antioxidant.		[10, 31]
	Lupeone	Anti-inflammatory, antiprotozoal, hepatoprotective, cancer preventive.		[10]
	Betulinic acid	Anti-inflammatory, antibacterial, antiviral, antidiabetic, antimalarial, antitumor		[10, 52]
Steroid	Stigmast-5-ene 3beta	Antidiabetic.		[10, 51]
Others	Physcion	Anti-proliferative.		[10, 53]
Others	Gibberellin	Anti-inflammatory.		[10, 54]

6. Pharmacological activities of S. apetala

6.1 Antioxidant Properties of S. apetala

Figure 2: Generalized mechanism of plant-derived antioxidant action

The imbalance between the production of reactive oxygen species (ROS) and the body’s antioxidant defenses is termed as Oxidative stress and it is a major factor in the development of chronic disorders like diabetes, liver damage, renal dysfunction [55]. Due to the multi-targeting potential of plant-based medicines, natural antioxidants have drawn a lot of interest as possible treatment for these disorders [56]. Several studies have already evaluated the antioxidant activity of Sonneratia apetala based on both in vitro and in vivo models.

DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)), FRAP (Ferric reducing antioxidant power) and other in vitro studies have revealed a strong dose-dependent antioxidant activity in the extracts of Sonneratia apetala, thus demonstrating its free radical scavenging potential [57]. In vivo studies provided further evidence of the antioxidant activities of Sonneratia apetala extracts as administering its extracts to experimental animal models showed an increase in the activities of antioxidant enzymes like glutathione peroxidase (GPx), catalase (CAT) and Superoxide dismutase (SOD). At the same time, it lowered lipid peroxidation indicators like malondialdehyde (MDA), suggesting that the tissues were protected from oxidative damage [58].

Polyphenols and other bioactive compounds are mainly responsible for these antioxidant effects as they can usually work in three ways: they scavenge the free radicals by giving them hydrogen atoms or electrons, chelate Fe2+ ions to stop the Fenton reaction from forming hydroxyl radicals, modulation of the expression of antioxidant enzymes to reinforce cellular defense [59]. The antioxidant activities of Sonneratia apetala observed throughout various studies are summarized in Table 3, which shows the types of extracts tested, experimental models used, assays employed and key outcomes of the tests. Overall, the compiled evidences demonstrated that S. apetala showed significant antioxidant potential across multiple experimental systems, providing a strong support for its antioxidant properties.

Table 3: Antioxidant properties of Sonneratia apetala extracts

Model	Treatment	Result	Ref.
In vitro. DPPH, NO free radical scavenging assay.	Pericarp methanolic extract.	Showed free radical scavenging activity.	[8]
In-vitro. Reducing power and DPPH radical scavenging activity.	Aqueous extract of fruit.	Showed high reducing power and DPPH radical scavenging activity.	[60]
In-vitro. Colorimetric method- Fe-chelating activity.	Fruit extract of n-hexane, chloroform, and methanol.	All fractions showed chelating activity. Methanolic fraction showed the highest activity with IC₅₀of 165 μg/mL.	[61]
In-vivo. Male Swiss albino mice- 100mg/kg I.P. injection of ferric carboxymaltose induced oxidative stress.	Methanol and n-hexane extract of fruit at 250, 500, 750, and 1000 μg/kg for 21 days.	Reduced iron profile; highest methanolic dose completely ameliorated blood and liver iron overload and prevented oxidative stress.	[61]
In-vitro. DPPH, ABTS, and NO radical scavenging activity.	Ethanolic fruit extract.	Showed strong scavenging activity against ABTS, DPPH and NO radicals.	[14]
In vitro. DPPH, NO, and ABTS scavenging; In vivo. Oxidative stress mice model.	Various fruit extracts (Pericarp methanolic, Aqueous, n-hexane, chloroform, methanol, and ethanolic).	Extracts showed radical scavenging, reducing power, and chelating; CHCl₃ excellent (IC₅₀ 13.76 μg/mL), n-Hex & EtOAc moderate (IC₅₀ 42.03 & 49.998); highest methanol dose prevented oxidative stress in iron-overloaded mice	[62]
In vitro. DPPH free radical scavenging method.	Methanol extract of leaf at concentrations of 5−80 μg/mL.	strong antioxidant activity (IC₅₀ of 41.92 μg/mL). IC₅₀ below 50 μg/mL means strong antioxidant activity.	[63]
In vitro assays including DPPH scavenging ability, NO free radical scavenging ability, and metal chelating ability	Methanol extracts of the fruit's seeds and pericarp	Seed extract showed stronger antioxidant activity than pericarp, with methanolic extract being the most effective.	[38]
In vitro: DPPH, NO free radical scavenging assay.	Pericarp methanolic extract.	Showed free radical scavenging activity	[64]
In-vitro: Reducing power and DPPH radical scavenging activity	Aqueous extract of fruit.	Showed high reducing power and DPPH radical scavenging activity	[64]
In vitro: Colorimetric method - Fe-chelating activity.	Fruit extract of n-hexane, chloroform, and methanol.	All fractions showed chelating activity. Methanolic fraction showed the highest activity with Ic50 of 165 μg/mL	[64]
In-vivo: Male Swiss albino mice - 100mg/kg I.P. injection of ferric carboxymaltose induced oxidative stress.	Methanol and n-hexane extract of fruit at 250, 500, 750, and 1000 μg/kg for 21 days.	Reduced iron profile; highest methanolic dose completely ameliorated blood and liver iron overload and prevented oxidative stress	[64]
In vitro antioxidant activity using DPPH and FRAP assays	Methanolic, ethanolic and aqueous extract of leaf	Methanolic leaf extract showed 77.37% scavenging, ethanolic 75.14%, and aqueous 68.12%	[65]
In vitro DPPH, reducing power, and total antioxidant capacity assays	Aqueous extract of S. apetala fruit powder	Strong antioxidant activity: IC₅₀ = 33.5 µg/mL (DPPH), reducing power = 170.83 mg GAE/g, total capacity = 210.43 mg AAE/g.	[66]
In vivo. PO/HX-induced hyperuricemic mice.	Aqueous extract of leaves, further concentrated with 60% ethanol	Restored renal SOD, CAT, GSH-Px and reduced MDA and ROS in kidney tissue; ↓UA, BUN, CRE, Cys-C; ameliorated kidney histological damage; ↓TNF-α, IL-6, IL-1β, COX-2, TGF-β1; ↑OAT1/3, ABCG2; ↓URAT1, GLUT9	[58]
In vitro (DPPH, ABTS⁺, NO, superoxide, hydroxyl radical scavenging, Reducing power)	Hydro-methanolic (20:80) extract of S. apetala leaves	strong in vitro antioxidant activity, effectively scavenging	[67]
In vivo (adult male Wistar albino rats)	Hydro-methanolic extract of Sonneratia apetala leaves	Exhibited antioxidant effects in gastric tissue by reducing lipid peroxidation and enhancing levels of glutathione and catalase	[67]
In vitro (chemical assays: DPPH, ABTS⁺, NO, O₂⁻, HO•, Reducing power	Aqueous extract of leaves and branches	Showed antioxidant activity (e.g., DPPH IC₅₀ = 0.81 mg/mL, ABTS⁺ IC₅₀ = 0.16 mg/mL, others)	[68]
In vivo (Kunming mice, HUA model)	Aqueous extract of leaves and branches (50, 100, 200 mg/kg) for 7 days	Dose-dependent ↑ SOD, CAT, GSH; ↓ MDA, ROS in kidney; strongest effect at 200 mg/kg, surpassing BZM (CAT/GSH) and FBX (GSH); indicates potent antioxidant activity	[68]
In vitro. DPPH, total phenolic, total flavonoid, and total antioxidant capacity assays.	Methanolic leaf extract of Sonneratia apetala	Exhibited antioxidant activity	[69]
In vitro. DPPH, H₂O₂, hydroxyl, and superoxide radical scavenging assays; total phenolic, flavonoid, and tannin content.	Ethanolic extract of pneumatophore (aerial root).	Strong free radical scavenging activity (IC₅₀: DPPH 71.77 µg/ml, H₂O₂ 97.27 mg/L, OH 79.62 mg/L, O₂⁻ 108.89 mg/L	[70]
In vivo. Oral glucose tolerance test (mice).	Ethanolic extract of pneumatophore at 250 & 500 mg/kg bw;	Significantly reduced blood glucose at 60 and 120 min; effect comparable to standard drug	[70]
In vitro. DPPH, nitric oxide (NO) free radical scavenging assay	Methanol fraction of seeds (MeS)	Strong antioxidant activity from polyphenols and vitamin C.	[12]
In vitro. Lipid-soluble antioxidant assay	n-Hexane fraction of seeds (HS)	Antioxidant activity from lipophilic compounds (ascorbyl palmitate, fatty acids).	[12]
In vitro antioxidant assays (DPPH, free radical scavenging)	Leaf extracts (Hexane, Ethyl acetate, Methanol)	Methanol extract showed strongest activity; ethyl acetate moderate; hexane weak.	[71]
In vitro. Total phenolic content, DPPH free radical scavenging assay	Crude extract, ethanol fraction, acetone fraction of S. apetala pneumatophores	Acetone fraction showed strongest antioxidant activity (IC50 2.4 μg/mL), ethanol fraction very low, crude extract moderate.	[72]
In vitro (DPPH, NO scavenging, reducing power, Fe²⁺ chelation, TAC)	Methanol, diethyl ether, chloroform, and ethyl acetate fractions of Sonneratia apetala seeds	Exhibited strong to moderate antioxidant activity; methanol seed fraction (MS) showed highest activity	[6]
In vitro: DPPH, reducing power, total antioxidant capacity (TAC), total phenolic content (TPC)	Seeds and pericarps; fresh and stored; uncooked or cooked (2–20 min); methanol extract of seeds	Antioxidant property: Seeds > pericarps; cooking seeds 20 min and pericarps 5–10 min gave highest activity; fresh > stored; methanol seed extract strongest	[73]
In vitro (DPPH, reducing power, Fe2+ chelation, TPC)	Methanolic extract of bark	methanolic bark extract showed strong antioxidant activity	[57]
In vitro antioxidant assays (DPPH, ABTS, NO scavenging, metal chelating, reducing power, total phenol, ascorbic acid, total antioxidant capacity)	Leaf and bark extracts (acetone, ethanol, methanol, aqueous)	Methanol leaf & bark: best DPPH, NO scavenging, reducing power; Ethanol bark: highest phenol & ascorbic acid; Ethanol leaf: highest total antioxidant capacity; metal chelating weak; overall strong antioxidant potential	[74]

6.2. Antidiabetic Effects of S. apetala

The characteristic trait of diabetes mellitus, a group of complex metabolic disorders, is persistent hyperglycemia brought upon by either insulin resistance, a reduced production of insulin or both [75]. Ultimately, chronic hyperglycemia causes fatal problems in the liver, kidney and cardiovascular systems by inducing oxidative stress, glycation end product formation and carbohydrate metabolism dysregulation. Seeing the limitations and side effects that current synthetic antidiabetic agents can give, plant derived natural products are now in the highlights and are being increasingly investigated as an alternative or complementary therapy due to their quality to act on multiple biochemical pathways simultaneously [76].

Figure 3: General antidiabetic mechanism of Sonneratia apetala extract

Sonneratia apetala has exhibited significant antidiabetic potential in both in vivo and in vitro models. In vitro models revealed that S. apetala extracts possessed potent inhibitory effects against carbohydrate digesting enzymes such as α-amylase and α-glucosidase, which delay the breakdown of carbohydrate and absorption of glucose [72, 74]. Furthermore, glucose uptake studies conducted using yeast models showed a dose dependent increase in the utilization of glucose, whereas glucose adsorption assays indicated that leaf extracts could bind to glucose molecules, consequently reducing their availability for absorption [77]. These findings together highlighted multiple mechanisms by which Sonneratia apetala can maintain or modulate blood glucose levels. In vivo studies further validated these outcomes as oral administration of the methanolic extract of fruit pericarp in streptozocin-induced diabetic rats, significantly reduced the fasting serum glucose over a prolonged treatment period [8]. Together these results suggest that both fruit and leaf derived extracts of S. apetala show hypoglycemic effects.

The antidiabetic activities of S. apetala observed across various experimental studies are summarized in Table 4, which shows the extract types, models used, and assays conducted as well as the key findings. Overall, the current evidence indicates that S. apetala holds a strong promise as a natural antidiabetic agent.

6.3 Reno-protective effects

Kidney dysfunction and chronic kidney disease are often linked to underlying metabolic disorders such as diabetic nephropathy and conditions characterized by systemic oxidative stress and chronic inflammation [79]. Given that Keora possesses potent antioxidant and anti-inflammatory properties and significant anti-diabetic effects, it can be strongly positioned to have potential reno-protective agent. Even though research dedicated to its direct reno-protective effects is currently limited, the existing evidence is quite compelling [58, 68, 80].

A key study investigating the effects of the aqueous extract of S. apetala in a hyperuricemia mouse model showed robust evidence for its reno-protective potential. Hyperuricemia is one of the known causes of oxidative stress and inflammation in the kidney, often leading to kidney stone formation and renal injury. Treatment with the leaf extract showed restored antioxidant defenses (enhanced activity of antioxidant enzymes like SOD, CAT, GSH) and reduced oxidative stress markers like MDA and reactive oxygen species [58]. Similarly, seed oil extracts, branch and leaf extracts have also shown improvement in antioxidant activity, renal histology and uric acid transporters, further confirming the reno-protective potential of S. apetala [65, 77].
The general mechanism of reno-protective action is illustrated in Figure 4, and the specific experimental findings are summarized in Table 5.

Table 4 : Antidiabetic Effects of Sonneratia apetala Extracts

Model	Treatment	Result	Ref.
In-vivo. Male Long-EVANS- STZ-induced type 2 DM rats.	Pericarp methanolic extract at 1.25g/10ml water/kg for 3 months.	↓Reduced serum glucose level	[8]
In-vitro. α-amylase and α-glucosidase inhibition.	10–1000 µg/mL (S. apetala fruit extract, in vitro)	Showed strong inhibitory activity of α-amylase and α-glucosidase. i.e. ↓ blood sugar absorption	[14]
In vivo. Oral Glucose Tolerance Test (OGTT) in Swiss Albino Mice	Methanolic extracts of 30 and 60 mg were administered; Blood samples were collected 120- and 180-min post-glucose administration.	↓ Blood glucose levels; Significant antidiabetic potential.	[64]
In vitro. Yeast cells (Saccharomyces cerevisiae)	Methanolic leaf extract of Sonneratia apetala (25–200 µg/mL)	↑ Increased glucose uptake in a dose-dependent manner; highest uptake at 200 µg/mL	[77]
In vitro. α-Amylase enzyme assay	Methanolic leaf extract of Sonneratia apetala (0.5–5 mg/mL)	↓ Inhibited α-amylase; near 100% inhibition at 2 mg/mL	[77]
In vitro. Glucose adsorption assay	Methanolic leaf extract of Sonneratia apetala (1%)	↑ Adsorbed glucose proportionally to concentration; maximum at 100 mmol/L	[77]
In vivo. Mice (oral glucose tolerance test)	Ethanolic extract of pneumatophores of Sonneratia apetala (250 & 500 mg/kg)	↓ Blood glucose significantly at 60 and 120 min;	[70]
In vitro. α-Glucosidase inhibition	Chloroform: Methanol (1:1) extract of leaves	↓ Inhibited α-glucosidase activity (IC₅₀ = 286 µg/mL)	[78]
In-vitro. α-amylase inhibition & Raphanus sativus root-growth inhibition	Pneumatophore crude methanol extract, ethanol fraction (95%), acetone fraction (50% acetone)	Crude: moderate α-amylase & root inhibition; Ethanol: low; Acetone: strong α-amylase & root inhibition (tannin-rich).	[72]
In vitro, Yeast α-glucosidase assay	Leaf & bark extracts: Acetone, Ethanol, Methanol, Aqueous	↓ Inhibited α-glucosidase activity in a dose-dependent manner; methanol extract most potent (both leaf and bark)	[74]

Figure 4: Flowchart illustrating the general reno-protective mechanism of S. apetala extracts

Figure 5: General Hepatoprotective mechanism of S. apetala Extract

Table 5 : Reno-protective effects of Sonneratia apetala extracts

Model	Treatment	Result	Ref.
In vivo PO/HX-induced hyperuricemic mice.	Aqueous extract of leaves, further concentrated with 60% ethanol	Restored renal SOD, CAT, GSH-Px and reduced MDA and ROS in kidney tissue; ↓UA, BUN, CRE, Cys-C; ameliorated kidney histological damage; ↓TNF-α, IL-6, IL-1β, COX-2, TGF-β1; ↑OAT1/3, ABCG2; ↓URAT1, GLUT9	[58]
In vivo. Potassium oxonate/hypoxanthine-induced hyperuricemic mice	Sonneratia apetala seed oil (SSO)	↓ Serum UA, CRE, and BUN. ↑ SOD, CAT, GSH-Px with ↓ ROS and MDA levels. ↓ Kidney histopathological lesions. ↓ MCP-1, IL-1B, IL-6, IL-18, TNF-a. maintained Protein expressions of GLUT9, URAT1, and OAT1 were reversed.	[80]
In vivo Hyperuricemia mice induced by Potassium oxonate (PO) and hypoxanthine (HX)	Aqueous extract of leaves and branches	↓ Kidney weight and index. ↓ Serum UA, CRE, and BUN. ↓ Kidney histopathological changes. ↓ MDA and ↑ CAT, SOD, and GSH. ↓ Renal inflammatory markers (IL-6, IL-18, IL-1ẞ, TNF-α, MCP-1, TGF-β). Regulated renal uric acid transporters (OAT1, URAT1, GLUT9).	[68]
In vivo Isoprenaline-induced male Long-Evans rats	Keora fruit peel extract 100 mg/kg/day	↓MDA, NO, and AOPP levels in the kidney ↑CAT, SOD, and GSH activity in the kidney ↓MPO activity in the kidney ↓Creatinine and uric acid levels	[81]

Table 6: Hepatoprotective effects of Sonneratia apetala extracts

Model	Treatment	Result	Ref.
In-vivo. Male Kunming mice- acetaminophen-induced liver injury.	Aqueous fruit extract at 100, 200, and 400mg/kg/day orally for 1 week.	↑ Survival, ameliorated liver histology, ↓ ALT, AST, MDA, TNF-α, IL-6, MPO; ↑ GSH, GSH-Px, CAT, total antioxidant capacity	[60]
In vivo: Male Swiss albino mice with iron overload induced by ferric carboxymaltose	In vivo: S. apetala fruit extract fractions (Hex, Chl, Met) at 100, 500, and 1,000 µg/kg bw daily for 15 days	All fractions (Hex, Chl, Met) showed dose-dependent amelioration of iron overload. Met was most effective, completely ameliorating iron overload	[61]
In vivo (Kunming mice, HUA model)	Aqueous extract of leaves and branches (50, 100, 200 mg/kg) for 7 days	↓ UA, CRE, and BUN in serum. ↓ XOD activity in the liver.	[68]
In vivo. PO/HX-induced hyperuricemic mice.	Aqueous extract of leaves, further concentrated with 60% ethanol	No hepatotoxicity; ↓ hepatic XOD and ADA activities	[58]

6.4 Hepatoprotective effects of S. apetala extract

Liver playing a crucial role in the metabolism and detoxification of substances like alcohol, drugs and metabolic byproducts makes it highly susceptible to injury and diseases, leading to conditions like NAFLD, fibrosis, or other metabolic disorders [82]. Hepatotoxicity is commonly associated with an elevated level of liver enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), lipid peroxidation, and inflammatory responses. Although synthetic hepatoprotective medications are available, prolonged use of such medicines may result in adverse side effects, which has led our researchers to the exploration of plant-derived natural products as alternatives or supplementary treatments [60, 61].

Sonneratia apetala has demonstrated significant hepatoprotective potential in various experimental models. In vivo studies using male Kunming mice with acetaminophen induced liver injury showed that the oral administration of the aqueous extract of fruit at 100, 200 and 400 mg/kg/day for 1 week significantly increased survival rats, ameliorated histological liver damage and also reduced the elevated levels of ALT, AST, malondialdehyde (MDA), TNF-α, IL-6 and myeloperoxidase (MPO). Alternatively, antioxidant markers including Glutathione (GSH), glutathione peroxidase (GSH-Px), catalase (CAT) and total antioxidant capacity were significantly increased, indicating a strong antioxidant and anti-inflammatory effects in the liver [60]. In addition to modulating oxidative stress, S. apetala extracts have also shown influence in purine metabolism by inhibiting hepatic xanthine oxidase (XOD) and adenosine deaminase (ADA), ultimately reducing the uric acid production and improving the renal-hepatic function in hyperuricemic mice models [58, 68]. Collectively, these findings portray the various ways S. apetala extracts can exert their protective effects on the liver. Figure 5 provides a comprehensive overview of S. apetala’s hepatoprotective effects. A comprehensive overview of different in vivo studies illustrating the hepatoprotective potential of S. apetala is provided in Table 6.

7. Toxicity and Safety

There is limited information regarding the toxicity and safety profile of Sonneratia apetala. Most of the in vivo study outcomes did not report any adverse outcomes, and the biochemical markers of hepatic and renal functions remained within normal ranges, suggesting tolerability at the tested doses [58, 60, 68]. However, a brine shrimp lethality bioassay showed cytotoxic potential in certain solvent fractions of the bark extract, highlighting that the extract may show toxicity based on the extraction method and plant part used [12]. Overall, while available data suggested relative safety in animal models, systemic acute, chronic, and subchronic toxicity studies are lacking. Future work should be done to address these gaps to establish a clear safety profile for potential therapeutic uses.

8. Future Perspective

This review provides a summary of the current scientific literature concerning the therapeutic potential of Sonneratia apetala (Keora). The findings showed that the diverse and potent pharmacological activities of this mangrove species are linked to its unique phytochemical composition [6]. The necessity for the plant to thrive under severe environmental stress has also driven it to evolve a robust defensive mechanism rich in polyphenols, flavonoids and triterpenoids [4]. The major pharmacological activities like antioxidant, antidiabetic, renoprotective and hepatoprotective effects for a unified therapeutic profile [3, 58]. The high antioxidant potential of Keora is its foundational activity acting as the molecular connection supporting its unique advantages against chronic diseases. For example, its robust antidiabetic and emerging reno-protective effects are not isolated activities but rather a direct consequence of its ability to mitigate oxidative stress and suppress chronic inflammation in tissues such as the liver and kidney [79]. The multi-targeting action of Keora, combining its anti-hyperglycemic effects with renal uric acid regulation, positions it as a promising candidate for managing metabolic syndrome and complications like diabetic nephropathy[58]. Despite these compelling preclinical findings, a major drawback is the limited research depth for certain effects. Therefore, future efforts must prioritize isolating lead compounds and validating these observations through further studies to fully understand their efficacy and safety profiles.

Although pharmacological evidence for Sonneratia apetala is promising, quite a large gap remains before it can be advanced towards clinical use. Most studies to date are limited to in vitro assays and small animal models, with little attention to pharmacokinetics, bioavailability, or long-term safety.

Future studies should thus focus on well-designed toxicity studies, analyses using modern molecular approaches and translational studies including clinical trials. Considering its rich and potent antioxidant and anti-inflammatory potential, evaluation in cardiovascular disease models such as myocardial infarction or cardiotoxicity models would also be valuable. With its broad phytochemical profile and efficacy against oxidative stress-driven disorders, S. apetala holds promise as a candidate for the development in Phyto-pharmaceutics.

9. Conclusion

Sonneratia apetala exhibits diverse pharmacological activities, including antioxidant, antidiabetic, reno-protective and hepato-protective effects, which can largely be credited to its rich phytochemical profile. While current findings are encouraging, most evidence is limited to preliminary in vitro and animal studies with little data on long-term safety or clinical efficacy. Further research should not only focus on standardization, toxicity and clinical validation but also extend to cardiovascular models, where its strong antioxidant and anti-inflammatory potential may reveal additional therapeutic applications.

Author Contributions

Conceptualization, MAA, NS.; methodology, SS, MA; software, SS, MAT; validation, HCG, FF; investigation, SS, MA; resources, MAA, MA, MTH; data curation, SS, MAT; FF; writing—original draft preparation, SS, MA, MAT, FF ; writing—review and editing, MA, HCG, MTH; visualization, SS; supervision, MA, NS. All authors have read and agreed to the published version of the manuscript.

Funding

This research did not receive any internal or external funding from profit and non-profit organizations.

Data Availability Statement

Data used in this study will be available upon reasonable request from the corresponding author.

Acknowledgments

The Authors gratefully acknowledge the logistic support from the Department of Pharmaceutical Sciences, North South University.

Conflicts of Interest

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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Figures

Author Affiliation

¹Department of Pharmaceutical Sciences, North South University, Dhaka, Bangladesh

^{2 School of Pharmacy, Brac University, Dhaka, Bangladesh}

ARTICLE INFO

Academic Editor

Dr. Raushanara Akter, Professor, School of Pharmacy, Brac University, Bangladesh

Received 13 August 2025

Accepted 30 November 2025

Published 20 December 2025

Article DOI

10.62624/JBEP00.0029

Corresponding author

Dr. Md. Ashraful Alam, Professor, Department of Pharmaceutical Sciences, North South University, Bangladesh