Alzheimer’s disease (AD) is the most prevalent type of dementia worldwide, constituting 70–80% of cases, primarily among the elderly. This irreversible neurodegenerative disorder progressively impairs memory and other cognitive functions. The molecular mechanisms of Syzygium species in neuroprotection include the inhibition of acetylcholinesterase (AChE) to correct cholinergic transmission, suppression of pro-inflammatory mediators, oxidative stress markers, RISreactive immediate species (RIS) production, enhancement of antioxidant enzymes, the restoration of brain ions homeostasis, the inhibition of microglial invasion, the modulation of ß-cell insulin release, the enhancement of lipid accumulation, glucose uptake, and adiponectin secretion via the activation of the insulin signaling pathway. Additional efforts are warranted to explore less studied species, including the Australian and Western Syzygium species. The effectiveness of the Syzygium genus in neuroprotective responses is markedly established, but further compound isolation, in silico, and clinical studies are demanded.
1. Anti-Cholinesterase Activity
Anti-cholinesterase activity remains the primary test used to screen anti-AD drug candidates.
Table 1 summarizes the anti-cholinesterase activities reported from
Syzygium species. They are often tested in vitro based on Ellman’s method using
acetylcholinesterase (AChE
) extracted from electric eel and butyrylcholinesterase (BChE) from equine serum. Nonetheless, efforts were made to determine in vitro activity using the parasite
Cotylophoron cotylophorum [34][1] and the fruit fly
Drosophila melanogaster [35][2]. Ex vivo AChE activity was also measured, revealing no significant activity from
S. cumini [36][3]. Apart from that, in vivo AChE and BchE activities were determined in alloxan-induced diabetic rats
[37][4] and scopolamine-induced memory-impaired rats
[29][5]. Both studies showed a significant reduction in enzyme activity.
To
the ourresearchers' best knowledge, about 10
Syzygium species were investigated for their anti-cholinesterase potential.
S. aromaticum (clove) represents the most studied
Syzygium species, followed by
S. cumini for this activity. Not only alcohol extracts were explored, but essential oils were also examined. Methanol and ethanol were widely used to extract
Syzygium species, while leaves were the most studied plant part for this bioactivity. Eugenol compound from clove demonstrated more potent inhibitory activity than its essential oil and extract, indicating this compound might provide major inhibition from this plant
[18][6]. Darusman et al. reported no significant activity from the leaf extract of
S. cumini [38][7], but other studies showed a disagreement. A reduction in cholinesterase activity was demonstrated from the essential oil, polyphenol-rich leaf extract as well as the seed extract of
S. cumini [22,29,37][4][5][8]. The inhibitory activity observed from essential oils of
Syzygium coriaceum,
S. cumini,
S. aromaticum, and
S. samarangense proposes their economic importance in therapy and nutrition
[22,27,39][8][9][10].
The aqueous extract of
S. jambos leaves revealed no significant activity
[30][11]. Similarly, the aqueous extract of clove buds exhibited very weak activity with >250 µg/mL of IC
50 [40][12], suggesting the unsuitability of water as a solvent for this analysis. Amir Rawa et al. reported the highest number of
Syzygium species (
Syzygium grande,
Syzygium lineatum,
S. jambos, and
S. polyanthum) exhibiting above 80% cholinesterase inhibition at 200 µg/mL concentration in one experiment
[41][13]. Among them,
S. polyanthum leaf extract showed the lowest IC
50 at 8.28 and 6.54 µg/mL against AchE and BchE, respectively. Further fractionation revealed that polar bioactive constituents (tannins and polyphenols) were accountable for the enzyme inhibition. It is noteworthy that the ethanol bud extract from
S. aromaticum corrected the AchE rate in cerium chloride (CeCl
3)-induced memory-impaired mice
[42][14]. This
res
tudyearch revealed a clear association between memory and AchE activity, where improved cholinergic neural transmission alleviated the state of memory in mice. Additional studies are required to confirm the bioactivity from other less known species of
Syzygium, but the potency of inhibiting cholinesterase from this genus is well established.
Table 1. Summary of anti-cholinesterase activities exerted from Syzygium species.
|
Species |
Plant Part/Compound |
Test |
Activity |
Reference |
1 |
Syzygium cumini | (L.) Skeels. |
Ethanol leaf extract |
In vitro AChE |
44.54 µg/mL of IC | 50 |
[36] | [3] |
Ex vivo AChE |
No significant effect |
Leaf essential oil |
In vitro AChE |
32.9 µg/mL of IC | 50 |
[22] | [8] |
Polyphenol-rich leaf extract |
In vitro AChE and BChE |
Significant reduction in cholinesterase activities; bound polyphenolic extract showed better inhibitory activity than free polyphenolic extract |
[37] | [4] |
Polyphenol-rich leaf extract |
In vivo AChE and BChE from alloxan-induced diabetic rats |
Enzyme activities were significantly reduced after 14 days (400 mg/kg oral dose) |
[37] | [4] |
Methanol seed extract |
In vivo AChE from scopolamine-induced rats |
Significant reduction in AChE activity (400 mg/kg oral dose) |
[29] | [5] |
Leaf extract |
In vitro AChE |
No significant activity |
[38] | [7] |
2 |
Syzygium aqueum | Alston |
Methanol leaf extract |
In vitro ACHE and BChE |
16.04 µg/mL and 13.95 µg/mL of IC | 50 | , respectively |
[43] | [15] |
3 |
Syzygium polyanthum | (Wight) Walp. |
Methanol and ethyl acetate extracts from leaves |
In vitro ACHE |
47.30 and 45.10 µg/mL of IC | 50 | , respectively |
[38] | [7] |
Methanol leaf and stem extracts |
In vitro ACHE and BChE |
>80% inhibition at 200 µg/mL concentration (8.28 and 6.54 µg/mL of IC | 50 | in the leaf extract, respectively) |
[41] | [13] |
4 |
Syzygium aromaticum | (L.) Merrill and Perry |
Methanol, ethyl acetate, and hexane extracts from leaves; methanol bud extract |
In vitro ACHE |
42.10, 55.9, and 62.05 µg/mL of IC | 50 | , respectively (leaves); 45.25 µg/mL of IC | 50 | (bud) |
[38] | [7] |
Methanol extract, clove oil, and eugenol |
In vitro ACHE and BChE using TLC bioautography |
Eugenol (42.44 and 63.51 µg/mL of IC | 50 | ) showed better inhibition than extract (61.5 and 103.53 µg/mL of IC | 50 | ) and oil (49.73 and 88.14 µg/mL of IC | 50 | ), respectively |
[18] | [6] |
Clove bud essential oil |
In vitro ACHE and BChE |
1.5 μL/L and 18.2 μL/L of IC | 50 | , respectively |
[27] | [9] |
Ethanol extract |
HPTLC-densitometry |
Showed efficiency in AChE inhibition |
[44] | [16] |
Ethanol bud extract |
In vitro AChE isolated from human erythrocytes |
No inhibitory effect |
[45] | [17] |
Ethanol bud extract |
In vitro AChE of parasite | C. cotylophorum |
86.86% inhibition at 0.5 mg/mL after 8 hr exposure |
[34] | [1] |
Clove oil (eugenol) encapsulated with a nanostructured lipid carrier |
In vitro ACHE and BChE from | D. melanogaster | tissue |
4.3 and 3.5 mM of IC | 50 | , respectively |
[35] | [2] |
Aqueous and hydroalcoholic extract of clove buds |
In vitro AChE |
253.29 µg/mL of IC | 50 | in aqueous extract |
[40] | [12] |
Clove oil |
In vitro AChE from AlCl | 3 | -induced rats |
Significant reduction in AChE activity |
[46] | [18] |
|
|
Ethanol bud extract |
In vivo AChE from CeCI | 3 | -induced memory-impaired rats |
Corrected the AChE rate caused by CeCI | 3 | toxicity and improved cholinergic neural transmission |
[42] | [14] |
|
|
Eugenol derivatives |
In vitro ACHE and BChE |
4-Allyl-2-methoxyphenyl-4-ethyl benzoate inhibited AChE with 5.64 µg/mL of IC | 50 |
[47] | [19] |
|
|
Isoeugenol |
In vitro ACHE |
77 nM of IC | 50 |
[48] | [20] |
5 |
Syzygium antisepticum | (Blume) Merr. and L.M.Perry |
Methanol leaf extract; ursolic acid; gallic acid |
In vitro ACHE |
61.9% at 300 µg/mL concentration; 81.64% at 200 µg/mL concentration; 73.39% at 200 µg/mL concentration |
[24] | [21] |
6 |
Syzygium samarangense | (Blume) Merr. and L.M.Perry |
Essential oil |
In vitro ACHE and BChE |
4.83 and 5.69 mg GALAE/g, respectively |
[39] | [10] |
Dihydrochalcone |
In vitro ACHE and BChE |
98.5% inhibition at 0.25 mM and 68% inhibition at 0.20 mM, respectively |
[49] | [22] |
7 |
Syzygium coriaceum | Bosser and J. Guého |
Essential oil |
In vitro ACHE and BChE |
4.79 and 7.10 mg GALAE/g, respectively |
[39] | [10] |
8 |
Syzygium jambos | (L.) Alston |
Aqueous leaf extract |
In vitro ACHE from homogenized tissue of rat brain |
No significant activity |
[30] | [11] |
Methanol stem and leaf extracts |
In vitro ACHE and BChE |
>80% inhibition at 200 µg/mL concentration (16.05 and 15.25 µg/mL of IC | 50 | from stem extract, respectively) |
[41] | [13] |
9 |
Syzygium grande | (Wight) Walp. |
Methanol leaf extract |
In vitro ACHE and BChE |
>80% inhibition at 200 µg/mL concentration |
[41] | [13] |
10 |
Syzygium lineatum | (DC.) Merr. and L.M.Perry |
Methanol leaf extract |
In vitro ACHE and BChE |
>80% inhibition at 200 µg/mL concentration (20.69 µg/mL of IC | 50 | for BChE) |
[41] | [13] |
2. Anti-Diabetic Activity
The most common form of diabetes, type 2 diabetes, is generally associated with hyperinsulinemia and insulin resistance. Insulin resistance causes neurodegeneration and impairment in the brain glucose metabolism and cognition, which are also observed in AD patients
[4][23]. Hyperinsulinemia increases tau phosphorylation and Aß accumulation. Furthermore, neuroinflammation, oxidative stress, mitochondrial dysfunction, and advanced glycation products are evident in diabetic and AD patients
[4][23]. Both disorders share similar features; medicinal plants that can stimulate insulin secretion would benefit diabetic as well as AD patients.
Zulcafli et al. extensively reviewed the anti-diabetic potential of eight
Syzygium species
[50][24].
TheIt's re
view reported that the inhibition of enzymes involving carbohydrate metabolisms such as α-glucosidase, maltase, and α-amylase is the most studied mechanism of action in the anti-diabetic potential of
Syzygium [50][24]. Pertaining to type 2 diabetes, the ethanolic seed extract of
S. cumini was shown to stimulate insulin secretion produced by pancreatic-ß cells in alloxan-induced mild and severely diabetic rabbits
[51][25]. The hydroethanolic extract from
S. cumini leaves also improved hyperinsulinemia and insulin resistance by modulating ß-cell insulin release in monosodium L-glutamate (MSG)-induced obese rats
[52][26]. Additionally, Sahana et al. demonstrated that a reduction in insulin resistance was evident in 30 newly diagnosed type 2 diabetic patients when
S. cumini seed powder was administered
[53][27]. The treatment of high-fat diet/streptozotocin (HFD/STZ)-induced diabetic rats with the aqueous seed extract of
S. cumini at 400 mg/kg decreased the levels of serum glucose, insulin, and other diabetic markers
[54][28].
A study by Shen et al. demonstrated a clear connection between insulin resistance and inflammation in TNF-α-treated FL83B cells
[55][29]. The suppression of c-Jun N-terminal kinase (JNK) inhibited an inflammatory response as the cells were treated with the fruit extract of
S. samarangense. As a result, insulin resistance induced by TNF-α was alleviated via the activation of phosphatidylinositol-3 kinase–protein kinase B (PI3K–Akt/PKB) signaling
[55][29].
S. aqueum leaf extract, on the other hand, reduced glucose levels, increased insulin secretion, and decreased the collagen deposition associated with its anti-inflammatory and antioxidant responses in STZ-induced diabetic rats
[56][30]. It decreased the levels of toll-like receptor 4 (TLR-4), myeloid differentiation primary response 88 (MYD88), TNF receptor-associated factor 6 (TRAF-6), and TNF-α correlated to pancreatic inflammatory cell infiltration. Malondialdehyde, a sensitive biomarker of ROS-induced lipid peroxidation, was also reduced
[56][30].
In another study, vescalagin isolated from
S. samarangense ameliorated insulin resistance in high-fructose diet-induced hyperglycemic rats
[57][31]. Myricitrin isolated from the
S. malaccense leaf extract exhibited insulin-like effects by enhancing lipid accumulation, glucose uptake, and adiponectin secretion via the activation of the insulin signaling pathway
[58][32]. The aqueous extract of
Syzygium paniculatum fruits alleviated hepatic insulin resistance at a 100 mg/kg dose by reducing the blockage of the insulin signaling pathway via the improvement of insulin receptor (IR and IRS-1) function in HFD-induced diabetic rats
[59][33]. In addition, the IR mRNA levels were restored to the control level in type-2 diabetic rats treated with
Syzygium jambolanum homeopathic remedies, suggesting improvement in insulin secretion
[60][34].
3. Anti-Inflammatory Activity
Nearly all pathological events, including endoplasmic reticulum stress and autophagy dysfunction, can trigger inflammatory responses in AD
[4][23]. Moroever, insulin resistance and diabetes have been shown to correlate well with inflammation. For example, the bark extract of
S. jambos improved the insulin receptor substrate-2/protein kinase B/glucose transporter-4 (IRS-2/AKT/GLUT4) insulin signaling pathway in the liver while improving glycemic parameters by suppressing inflammation, oxidative stress, and apoptosis in STZ-induced rats
[61][35]. Inflammation is defined as a physiological defense mechanism by the immune system to combat health hazards, causing pain to occur
[4][23]. It was demonstrated that microglia accumulate in higher quantities near Aß plaques than in the healthy brain. Amyloid plaques and other factors can activate microglia to initiate neuroinflammation
[4][23]. Anti-inflammatory drugs enable the central nervous system (CNS) to impede pain signaling in the brain, therefore, reducing inflammation in AD pathogenesis. Recent anti-inflammatory activities reported from
Syzygium were summarized in
Table 2.
The levels of pro-inflammatory mediators such as IL-6, IL-1β, and TNF-α were generally measured to determine the anti-inflammatory activity (
Table 2). The inflammation was induced by a toxic chemical or drug such as alloxan and STZ to stimulate inflammatory diabetes in model rats. LPS- or HFD-induced inflammation in diabetic rats was also conducted to observe the anti-inflammatory potential of
Syzygium. So far, one study has demonstrated a close correlation between inflammation and memory loss in AD model rats. The memory-related learning ability of Aβ
1-40-infused AD model rats was improved as pro-inflammatory TNF-α and lipid peroxide (LPO) were suppressed when
S. cumini seed extract was administered
[62][36]. The leaf, fruit, pulp, and seed extracts of
S. cumini exerting anti-inflammatory activity suggested that almost all parts are bioactive (
Table 2).
S. malaccense leaf extract exerted neuroinflammatory protection against LPS-induced neuroinflammation on murine BV-2 microglial cell lines by reducing nitric oxide production
[63][37]. Nitric oxide (NO) is one of the pro-inflammatory mediators released by microglia; reducing the NO levels can minimize immune outrage caused by microglia
[4][23]. Other less studied
Syzygium species have also been observed to exert anti-inflammatory activities, including
Syzygium caryophyllatum,
Syzygium mundagam,
Syzygium calophyllifolium, and
S. samarangense (
Table 2).
Table 2. Summary of anti-inflammatory activities reported from Syzygium species.
|
Species |
Plant Part/Compound |
Test |
Activity |
Reference |
1 |
S. malaccense | (L.) Merr. and L.M. Perry |
Methanol leaf extract |
In vitro LPS-induced neuroinflammatory assay on murine BV-2 microglial cells; in vivo croton oil-induced ear edema test |
Neuroprotective activity by a reduction in nitric oxide production in vitro; decreased mice ear edema in vivo |
[63] | [37] |
2 |
S. cumini |
Methanol fruit extract |
In vitro membrane stabilization, egg albumin denaturation, and bovine serum albumin denaturation assays; in vivo murine models of carrageenan, formaldehyde, and PGE | 2 | induced paw edema. |
Showed inflammatory activities both in vitro and in vivo |
[64] | [38] |
|
|
Betulinic acid |
In vivo Fx1A antiserum-induced passive Heymann nephritis (PHN) in Sprague-Dawley rats |
S. aromaticum (clove) is indeed the most studied
Syzygium species for its antioxidant capacity. Its economically important essential oil source has brought many interests toward its applications. Alfikri et al. reported that clove produced the best essential oil ingredient at the flowering stage and the most efficient source of antioxidants when the trees are young.
[86][60]. Meanwhile, Teles et al. demonstrated that eugenol (the primary compound of clove oil) exhibited higher antioxidant activity than its essential oil
[87][61]. Various plant parts of the clove have been examined, especially its bud essential oil (
Table 3). As for
S. cumini and
S. malaccense, their dried peel powders showed higher phenolic compounds, anthocyanin content, and antioxidant activity than their freeze-dried extracts, which can be pharmacologically relevant to their food applications
[88][62].
Table 3. Summary of plant parts or compounds examined for antioxidant activity from Syzygium species.
|
Species |
Plant Part/Compound |
Reference |
1 |
S. cumini |
Leaf |
[36,37,89] | [3][4][63] |
|
|
Fruit |
[64,88,90] | [38][62][64] |
Ameliorated mRNA and protein expression of NF-κB, iNOS, TNF-α, Nrf2, HO-1, and NQO1 in the kidney, reducing inflammation |
[ | 65 | ] | [ | 39] |
|
|
Bark |
[91] | [65] |
|
|
Polyphenol-rich leaf extract |
In vivo Alloxan-induced diabetic rats |
NF-κB and inflammatory cytokines such as TNF-α and IL-1α were regulated |
|
|
Polyphenol-rich extract |
[92,93] | [66][67] | [37] | [4] |
|
|
Anthocyanins di-glucosides from pulp |
In vitro determination of cytokine production in LPS-induced RAW264.7 macrophages |
Inhibited pro-inflammatory mediators such as IL-6, IL-1β, and TNF-α |
[66] | [40] |
|
|
Seed kernels powder |
[94] | [68] |
|
|
Aqueous seed extract |
In vivo high cholesterol diet-streptozotocin-induced diabetes in rats |
Exhibited significant anti-inflammatory and β-cell salvaging activity via overexpression of PPARγ and PPARα activity and a significant decrease in TNF-α levels when treated with 100, 200, 400 mg/kg/day doses |
[67] | [41] |
2 |
S. polyanthum |
Leaf |
[38] | [7] |
|
|
3 | Methanol seed extract |
In vitro high glucose (HG) diabetic cardiomyopathy in | H9C2 cardiomyoblast cells |
S. aromaticum | HG-induced activation of NF- | κ | B, TNF- | α | , and IL-6 was remarkably reduced |
[ |
Flower | 68] | [42] |
[ | 86 | ] | [60] |
|
| |
| Seed extract |
In vivo Aβ | 1-40 | -infused AD model rats |
Reduced the levels of Aß burdens and oligomers by suppressing the levels of TNFα and LPO in the corticohippocampal tissues |
[62] | [36] |
Bud |
[ | 42 | ,95] | [14][69] |
3 |
Syzygium caryophyllatum | (L.) Alston |
Aqueous root extract |
In vitro anti-inflammatory test using heat-induced albumin denaturation assay |
6.229 µg/mL of IC | 50 |
[69] | [43] |
|
|
Bud essential oil |
[27,86,,98] | [9 | 87, | ][60 | 96, | ][61][70] | 97 | [71][72] |
4 |
S. aqueum |
Polyphenol-rich leaf extract |
In vitro lipoxygenase inhibitor screening assay, membrane stabilizing activity (hypotonic solution-induced hemolysis), and in vivo carrageenan-induced hind-paw edema in rats |
Inhibited LOX, COX-1, and COX-2 with higher COX-2 selectivity reduced the extent of lysis of erythrocytes and markedly reduced leukocyte numbers in rats challenged with carrageenan. |
[ |
|
|
Eugenol |
[87] | [61] | 70] | [44] |
|
|
| Leaf extract |
In vivo STZ-induced oxidative stress and inflammation in pancreatic beta cells in rats |
Significantly decreased levels of TLR-4, MYD88, pro-inflammatory cytokines TNF-α, and TRAF-6 in pancreatic tissue homogenates, which correlated well with minimal pancreatic inflammatory cell infiltration |
|
All parts |
[99] | [73] | [56] | [30] |
5 |
Syzygium mundagam | (Bourd.) Chithra |
Methanol bark extract |
In vivo carrageenin- and egg albumin-induced paw edema, cotton pellet implanted granuloma in rats |
Effective anti-inflammation at 200 mg/kg dose |
[ |
4 | 71 | ] | [ | 45 | ] |
S. | antisepticum |
Leaf |
[24] | [21] |
6 |
Syzygium calophyllifolium (Wight) Walp. |
Methanol bark extract |
In vivo carrageenin- and egg albumin-induced paw edema, cotton pellet implanted granuloma |
200 mg/kg dose significantly reduced the paw edema in carrageenan (96.71%) and egg albumin models (54.24%) compared to the control. Chronic inflammation was also inhibited by up to 70.46% |
[] | [46] |
|
|
Gallic acid, myricitrin, and quercitrin |
[24] | [21] | 72 |
7 |
S. aromaticum |
Ethanol/water extract |
In vivo carrageenan-induced paw edema inflammatory in rats |
Pretreatment at different doses (100, 200, and 400 mg/kg) produced a significant ( | p | < 0.001) reduction in paw inflammation up to 5 h of carrageenan injection |
5 | [ | 73 |
S. caryophyllatum | ] | [47] |
Leaf |
[ | 100 | ] | [74] |
|
|
Essential oil |
| In vivo formalin-induced and carrageenan-induced paw edema inflammation in rats |
|
Fruit |
[100,101] | [74][ | 26.9 ± 2.5 μg/paw of EC | 50 |
[74] | [48] |
75 | ] |
|
|
Aqueous clove extract |
In vivo LPS-induced lung inflammation in mice. |
Inhibited matrix metalloproteinases: MMP-2 (15%) and MMP-9 (18%) activity in lung homogenates, reducing inflammation |
[75] | [49] |
|
|
|
Fruit pulp healthy snack |
[102] | [ | |
Ethanol extract |
In vitro TNF-α induced inflammation in dental pulp stem cells |
Prevented the increase in IL-6 levels |
[76] | [50] |
76 | ] |
6 |
Syzygium paniculatum | Gaertn. |
Leaf |
[103] | [77] |
|
|
| Eugenol |
|
Fruit | Cytochrome c reduction assay to measure superoxide anion generation in human neutrophils |
[104] | [ | Inhibited the generation of superoxide anion by neutrophils via the inhibition of Raf/MEK/ERK1/2/p47phox-phosphorylation pathway |
78] | [77] | [51] |
|
|
Eugenol |
|
|
Volatile oil from the aerial part | In vivo ethanol-induced ulcer in rats |
Decreased TNF-α and IL-6 cytokine concentrations responsible for inflammation |
[105] | [79] | [78] | [52] |
|
|
Essential oil |
Isbolographic study using the formalin test in rats |
S. aromaticum | in combination with ketorolac, showed an antinociceptive effect in the treatment of inflammatory pain |
[79] | [53] |
7 |
S. malaccense |
Leaf |
[63,88,106] | [37][62][80] |
8 |
S. samarangense |
Polyphenol vescalagin |
In vivo methylglyoxal-induced inflammation in diabetic rats |
The pancreatic levels of NF-κB, ICAM-1, and TNF-α protein, were reduced |
[80 |
|
|
Myricetin derivatives |
[107] | ] | [54] |
[ | 81 | ] |
|
|
Lyophilized fruit powder |
In vivo STZ-induced pancreatic beta cells apoptosis in rats |
Pancreatic ß-cell apoptosis was alleviated with significantly down-regulated cleaved caspase-3 and Bax and upregulated Bcl-2 and Bcl-xl protein expression |
[81] | [55] |
8 |
S. aqueum |
Stem |
[108] | [82 |
9 |
S. polyanthum |
Leaf extract |
In vivo coronary artery ligation-induced myocardial infarction in rats |
Reduced levels of C-reactive protein (CRP) and myeloperoxidase (MPO) in the rats started from day 4 after the induction of myocardial infarction. |
[82] | [56] |
10 |
S. jambos |
Bark extract |
In vivo streptozotocin-induced inflammation in diabetic rats |
Significantly reduced TNF-α and increased IL-10 ( | p | < 0.05) in pancreatic tissues |
[61] | [35] |
4. Antioxidant Activity
Oxidative stress is highly apparent when redox circuitry is disrupted, and macromolecular damage occurs, leading to an imbalance in the pro-oxidant and antioxidant levels
[83][57]. The overproduction of RIS, such as hydrogen peroxide (H
2O
2), hydroxyl radical (HO), and NO observed in the AD brain, can trigger severe oxidative stress. Various factors can contribute to excessive RIS, including mitochondrial dysfunction, high levels of cytochrome oxidase, and Aß peptide chelation by redox-active metal ions
[4,83][23][57]. Moreover, the downregulation of the expression and activity of antioxidant enzymes such as dehydrogenase complexes is evident in AD, causing biomolecular damage (lipids, proteins, and DNA) and neuronal death
[4][23]. Antioxidants help scavenge free radicals and balance the production of RIS to reduce oxidative damage
[84][58].
Syzygium is undeniably a great source of antioxidant agents due to the presence of polyphenols, tannins, and flavonoids
[84][58]. The evidence of antioxidant activities from
Syzygium species was summed up in
Table 3. Compared to other biological activities, the antioxidant potential is the most comprehensively explored in various
Syzygium species, including less studied
Syzygium cymosum,
S. paniculatum, and
S. caryophyllatum. They not only scavenge free radicals but also provide protective effects against other toxicities. For example, CeCl
3-induced neurotoxicity in the brains of rats was improved by the antioxidant capacity of
S. aromaticum to restore RIS levels, which alleviated the cholinergic neural transmission and the state of memory in mice
[42][14]. In another study, the ability of antioxidants to maintain genomic stability and slow down aging was demonstrated in the
Caenorhabditis elegans nematode model
[85][59]. The essential oil of
S. aromaticum exerted antioxidant potential by inducing the expression of SOD-3 or GST-4 (antioxidant enzymes) and DAF-16/FOXO nuclear translocation from the cytoplasm to promote longevity in
C. elegans [85][59].
] |
|
|
Bark |
[ |
108 |
] |
[ |
82 |
] |
9 |
S. polyanthum |
Leaf |
[ | 109 | ] | [83] |
10 |
S. jambos |
Fruit |
[110] | [84] |
|
|
Bark |
[61] | [35] |
11 |
S. samarangense |
Vescalagin |
[80] | [54] |
12 |
Syzygiumcymosum | (Lam.) DC. |
Leaf |
[111] | [85] |