To date, only few literatures have reported the toxicity of the plant. The leaf extract of S. jambos is safe at a dose up to 5 g/kg b.wt. assessed by the acute toxicity test (Dhanabalan and Devakumar, 2014). The toxicity of the methanol extract of S. jambos and its fraction were evaluated by shrimp lethality bioassay. Methanolic extract and carbon tetrachloride fraction displayed significant lethality with LC₅₀ = 6.97 and 13.61 µg/ml, respectively. Whereas the chloroform and hexane fractions showed moderate to low lethality with LC₅₀ = 64.94 µg/ml and 257.6 µg/ml, respectively (Haque, 2015). In the same line, Ghareeb et al. (2016) tested different extracts and fraction obtained from the leaves and flowers against the brine shrimp Artemia salina, a useful tool to determine the toxicity of natural products. As a result, the n-butanol fraction of the leaves showed a strong toxicity with LC₅₀ = 50.11 µg/ml while the dichloromethane and petroleum ether fractions were less toxic (LC₅₀ = 446.65 µg/ml) (Ghareeb et al., 2016).

Toxicology safety evaluation is essential for plants applications and new drug development. However, the toxicological studies of extracts and compounds isolated from S. Jambos have not been fully explored yet. Therefore, further research in toxicity is needed to determine the suitability of the plant extracts and related compounds composition.

Diverse antimicrobial activity of crude extracts and isolated compounds from the plant were described in previous reports. Disc diffusion assays, agar well diffusion, and broth microdilution procedures were employed to assess the antibacterial activity of plant extracts. As shown in Table 2. Microbial growth inhibition zones and percentages, as well as minimum inhibitory concentrations (MICs), demonstrated that S. jambos has potential as a significant antibacterial agent.

Wamba et al. (2018) reported the capacity of S. jambos extracts to increase the potency of chloramphenicol antibiotic towards bacteria strains expressing MDR phenotype (Wamba et al., 2018). Leaf and bark extracts of the plant expressed up to 70% of antibiotic-modulating activity against S. aureus strains at MIC/2. Similar results were obtained in association with tetracycline, ciprofloxacin, and erythromycin against Gram-negative bacteria including strains of Escherichia coli (AG100ATet, AG102), Enterobacter aerogenes (EA27, EA289), Klebsiella pneumoniae (KP55, KP63), Providencia stuartii (PS299645, NEA16) and Pseudomonas aeruginosa (PA01, PA124) (Wamba et al., 2018). Likewise, S. jambos leaf extracts demonstrated potent antiviral effects on the virus involved in vesicular stomatitis and against different types of herpes simplex virus (Abad et al., 1997; Athikomkulchai et al., 2008).

Isolated compounds friedelin, β-amyrin acetate, betulinic acid, and lupeol, from the bark extract, were tested for their antidermatophytic activity against three commonly dermatophyte species found in Cameroon namely Microsporum audouinii, Trichophyton mentagrophytes and T. soudanense. Betulinic acid and friedelolactone were the most active compounds with MIC ranging from 12.5 to 100 µg/ml and the most sensitive fungi were Trichophyton soudanense (MIC = 25 µg/ml) and Trichophyton mentagrophytes (12.5 µg/ml) (Kuiate et al., 2007). The phenolic compounds, quercetin, rutin, prenylbenzoic acid 4-O-β-D-glucopyranoside, morolic acid 3-O-caffeate, 5,4′-dihydroxy-7-methoxy-6-methylflavone, 3,4,5-trihydroxybenzoic acid, isoetin-7-O-β-D-glucopyranoside, and (4′-hydroxy-3′-methoxyphenol-β-D-[6-O-(4″-hydroxy-3″,5″-dimethoxylbenzoate)] glucopyranoside) also exhibited both antibacterial and antifungal potentials with a diameter of inhibition zones ranging from 9–19 mm (Ghareeb et al., 2017). Accordingly, the antimicrobial activity of S. jambos crude extracts have been related to the presence of an increased level of tannins in the preparation (Baliga et al., 2017).

Moreover, silver nanoparticles synthetized from leaves and bark extracts of S. jambos showed higher antiplasmodial activity against chloroquine sensitive and resistant strains of Plasmodium falciparum (Dutta et al., 2017). The fatty compounds, ethyl linoleate, methyl linolenate and phytol, inhibited the QS-dependent pigment production in C. violaceum and lowered pyoverdine production in P. aeruginosa as well. Results were also confirmed by docking analysis (Musthafa et al., 2017). The above research confirmed the antimicrobial activity of S. jambos. However, it is worthy to note that the above studies focused on the in vitro evaluations. Consequently, these studies only give preliminary information about the activity of S. jambos. Therefore, further studies combining in vivo and in vitro need to be conducted to provide reliable basis for exploring new potentially and low toxic antimicrobial agents from the studied plant.

Several studies, both in vitro and in vivo, reported the antioxidant activity of S. jambos extracts and its phytochemicals. Bonfanti et al. (2013) demonstrated the potency of the leaf aqueous extract of S. jambos to inhibit the nitric oxide radical, the lipid peroxidation and the mitigation sodium-nitroprusside-induced oxidative stress in rats. The extract also showed a capacity to increase the GSH levels in rats (Sobeh et al., 2018). Furthermore, the bark extract inhibited lipid peroxidation and increased reduced glutathione (GSH) in pancreatic tissues of STZ-diabetic rats (Mahmoud et al., 2021). S. jambos leaf extract abolished ROS production by endothelin-1 in human polymorphonuclear and mononuclear cell migration (Inostroza-Nieves et al., 2021). On the other hand, S. jambos rich phenolic and flavonoid fractions demonstrated good antioxidant activities as shown in Table 3. The chalcones phloretin 4′-O-methyl ether, myrigalones B and G were assessed for their antioxidant activity using DPPH radical. As a result, myrigalone B showed a significant capacity of scavenging radicals with an IC₅₀ of 3.8 µg/ml while the other compounds showed low to moderate activity (IC₅₀ > 30 µg/ml) (Jayasinghe et al., 2007). Moreover, 2,6-dihydroxy-4-methoxy-3,5-dimethyldihydrochalcone showed anti-DPPH activity with an IC₅₀ value of 10.6 µg/ml while, the flavones, 4′-methoxysideroxylin and 6-demethylsideroxylin, and phloroglucinols, jambones A-B, presented weak antioxidant activities in FRAP and DPPH radical scavenging activities (Li et al., 2015).

There are relatively few studies on neuroprotective effect of S. jambos. Bonfanti et al. (2013) investigated the effects of S. jambos in the inhibition of both AChE and BuCE, the two main enzymes in the occurrence of Alzheimer. As a result, the aqueous leaves extract of S. jambos showed significant AChE (IC₅₀ = 16.5 µg/ml) and BuCE (IC₅₀ = 15.2 µg/ml) inhibition potentials in support with the uses of the plant to alleviate Alzheimer disorders. Considering these findings, further investigations may improve the neuroprotective effect of S. jambos.

In vitro anticancer activity of isolates from S. jambos was determined towards various cancer cell lines, providing data on the bioactivity of both extract and single compounds, Table 3 . Methanolic extract of S. jambos leaves showed cytotoxic effects against liver cancer cell line, Hep G2 cells, by inducing apoptotic pathways (Thamizh Selvam et al., 2016). Moreover, another study evaluated the anticancer effects of the leaves along with other extracts on human melanoma (A375), epidermoid carcinoma (A431), cervical epithelial carcinoma (HeLa) and human embryonic kidney cells (HEK-293). They found that the extract showed low toxicity against HEK-293 cells but better effects against A431 and HeLa cells (IC₅₀ = 34.90–56.20 μg/ml) (Twilley et al., 2017). The hydrolysable tannins, 1-O-galloyl castalagin and casuarinin, exhibited significant cytotoxic activity against the human promyelocytic leukemia cell line HL-60 with IC₅₀ of 10.8–12.5 µM and showed moderate to low cytotoxicity on the human adenocarcinoma SK-HEP-1, normal cell lines of human lymphocytes and liver cell lines. Results were confirmed by DNA fragmentation assay and microscopic investigation of cells (Yang et al., 2000). The cytotoxic effects of the phenolic compounds, cis-3-p-coumaroylalphitolic acid and 4′-methoxysideroxylin, on melanoma SK-MEL-28 and SK-MEL-110 cell lines were assessed as well as that of the normal Vero cells, following the MTT assay. The compounds, displayed potent effects on the two melanoma cells with IC₅₀ ranging from 18.3–81.5 µM (Li et al., 2015). The cytotoxic effect of quercetin-3-O-β-D-xylofuranosyl-(1 → 2)-α-L-rhamnopyranoside and myricetin-3-O-β-D-xylofuranosyl-(1 → 2)-α-L-rhamnopyranoside isolated from the CH₂Cl₂/MeOH fraction of the plant was evaluated against RW 264.7 cell lines. Both flavonoids demonstrated a moderate activity (IC₅₀ = 1.68 and 1.11 µM, respectively) (Ticona et al., 2021). The cytotoxic effect of the nanoparticles synthetized from the leaf and bark extracts of S. jambos was assessed against HeLa and L6 cells using MTT assay. As a result, the nanoparticles were found to be non-toxic toward HeLa and L6 cell lines (Dutta et al., 2017). These investigations provided the anticancer potential of S. jambos, further in vivo, toxicological, and clinical studies are needed in future to guarantee efficiency and safety.

Inflammation and specifically low-grade inflammation play a vital role in many diseases. Natural products with anti-inflammatory effects are promising targets for drug discovery. In vitro and in vivo models were applied to determine the anti-inflammatory effects of crude extracts and pure compounds from S. jambos. In vitro studies showed that the ethanol leaf extract of S. jambos and the commercially available chemicals ursolic acid and myricitrin dramatically reduced the release of inflammatory cytokines IL 8 and TNF-α by 74–99% indicating anti acne effects (Sharma et al., 2013). A more recent study on two isolated glycosylated flavonoids, the quercetin-3-O-β-D-xylofuranosyl-(1 → 2)-α-L-rhamnopyranoside and myricetin-3-O-β-D-xylofuranosyl-(1 → 2)-α-L-rhamnopyranoside, isolated from the chloroform/methanol fraction of S. jambos showed that they reduced the production of TNF-α, with IC₅₀ values of 1.68 and 1.11 M, respectively in the RAW 264.7 cell line. In addition, at a dose of 5 mg/kg, the flavonoids reduced the levels of TNF-α, C-reactive protein, and fibrinogen in murine models (Apaza Ticona et al., 2021). In vivo studies showed that the ethanol extract of the leaves also exerted potent anti-inflammatory effects at a dose of 400 mg/kg in carrageenan and histamine edema rat models (Hossain et al., 2016). The soluble fraction of polysaccharide fraction of the plant also expressed a capacity to increase the secretion of TNF-α, IL-1β and IL-10 in a concentration-dependent manner (10–100 µg/ml). The aqueous extract of the plant attenuated the inflammatory response induced by LPS at a concentration of 100 µg/ml (Tamiello et al., 2018b). Furthermore, the bark extract inhibited pancreatic inflammation in STZ diabetic rat model where it dose-dependently suppressed the pro-inflammatory, TNF-α and increased the anti-inflammatory IL-10 levels (Mahmoud et al., 2021).

Liver is one of the largest and important organs in human body and performs numerous interrelated vital functions, such as metabolism, biotransformation, and detoxification of toxins. Consequently, liver diseases resulting from liver damage is a global problem. Herbal medicine has been used traditionally for the prevention of liver diseases (Islam et al., 2012). Preclinical studies have shown that extracts from different parts of S. jambos possess beneficial effect in liver related diseases, Table 4. The methanol extract of the leaves of the plant significantly modulated the levels of liver biochemical parameters ALT, AST, MDA, TB, TC, TG, GSH and SOD) in comparison with the positive control, silymarin, Table 4 (Sobeh et al., 2018). Isolation of the compounds of the extract may led to the discovery of promising active constituents.

Diabetes and diabetic complications are global health problem. Although many medicinal plants were investigated for their possible antidiabetic activities, there are relatively few studies on antidiabetic effect of S. jambos extracts. An in vitro study compared the inhibitory effects of ethanol extract of different organs of S. jambos on α-glycosidase and α-amylase activities, enzymes related to diabetes, and showed that the inhibitory effects against yeast and mice intestinal α-glucosidase activity was on the following order: seed ˃ stem ˃ leaf ˃ root ˃ flower ˃ flesh ˃ acarbose, while the inhibitory effect on α-amylase activity was acarbose ˃ seed ˃ stem ˃ root ˃ leaf ˃ flesh ˃ flower (Wen et al., 2019). In vivo studies showed that the infusion of the combined leaves of S. jambos and S. cumini had no significant effect on blood glucose levels in a randomized double-blind clinical trial in non-diabetic and diabetic subjects (Teixeira et al., 1990). However a more recent study showed that the ethanol extract of leaves at two dose levels (374.5 mg/kg and 749 mg/kg, Po) lowered blood glucose levels in alloxan induced diabetic rabbits (Prastiwi et al., 2019). Moreover, an aqueous leaf extract from the plant showed better blood modulation potential of glucose over time, in diabetes genetic mouse models (Gavillán-Suárez et al., 2015). Recent studies have shown the protective effect of the bark extract on pancreatic β cells against streptozotocin-induced diabetes. The extract have also improved insulin signaling pathway in the liver and glycemic parameters and have suppressed pancreatic oxidative stress (Mahmoud et al., 2021). However, further studies need to be conducted to confirm the potential of S. jambos as a natural antidiabetic agent, as it can be incorporated into functional foods and nutraceutical products.

The antiurolithiatic activity of the leaf extract of S. jambos, collected in India, was evaluated both in vitro and in vivo using ethylene glycol induced urolithiatic model in rats. Results showed a capability of the extract to prevent the growth of urinary stones. However, further studies should be done to understand the mechanism and pharmacological action in preventing urolithiasis in susceptible populations (Deka et al., 2021).