INTRODUCTION:

Ziziphus belongs to the Rhamnaceae Family, comprising around 170 species distributed globally. Some species of this genus have long been utilized as valuable commodities and traditional medicines in various regions, including Africa, Asia, and South America. Many studies have been conducted on numerous species of this genus, particularly within agriculture, food chemistry, and medicinal plants. Some of them aimed to characterize the metabolites present in these plants and explore their associated pharmacological properties.^1,2

Ziziphus jujuba is a widely studied species within the Ziziphus genus, particularly significant in China where its fruit is both a staple food and a common flavoring agent. It holds importance in Traditional Chinese Medicine (TCM) as well. With approximately 1.5 million hectares dedicated to its cultivation, Z. jujuba fruit is a crucial economic commodity in China, producing around 2.5 million tons annually and exported to numerous countries^3,4. Extensive preclinical and clinical trials have been conducted on Z. jujuba, revealing its diverse bioactivities including antioxidant, hepatoprotective, analgesic, anti-inflammatory, antiepileptic, and anti-cancer properties^5-11. Additionally, Z. jujuba seeds exhibit anxiolytic, hypnotic-sedative, neural protection, anti-inflammatory, and dyslipidemia effects^9,12-17. Clinical studies have explored its efficacy in treating conditions such as neonatal jaundice, dyslipidemia, adolescent obesity, constipation, menopausal symptoms, and insomnia^18-22.

Ziziphus mauritiana (Indian jujube or ber) is native to South Asia and widely distributed in countries like India, Pakistan, Bangladesh, and Sri Lanka. It holds cultural significance in various South Asian traditions and is used in traditional medicine for its potential health benefits. The fruit, leaves, and bark of Z. mauritiana are utilized to treat various ailments, including digestive issues, respiratory problems, hepatoprotective, and skin conditions^23-26. Studies have shown antioxidant properties in the leaves^27,28 and anti-obesity activity in the bark by inhibiting pancreatic lipase²⁹. Ziziphus spina-christi, originating from the Middle East and North Africa, boasts a long history of traditional medicinal use for various ailments^30,31. Its reported bioactivities include anti-obesity, antibacterial, antioxidant, antimicrobial, and anti-inflammatory properties^23,27,29-32. Ziziphus lotus, found in the Middle East, Africa, and Europe, is recognized for antioxidant, antibacterial, tyrosinase inhibitor, and anticancer effects ^33-35. Ziziphus joazeiro, native to South America, particularly Brazil, has garnered attention for its antioxidant, antibacterial, antifungal, and antiparasitic properties^36-38.

Research on phytochemicals and their bioactivity within the genus Ziziphus has evolved from traditional activity testing of extracts to advanced metabolomics approaches. Metabolomics offers a comprehensive and efficient means of exploring active compounds, accelerating natural product research. Particularly valuable within the diverse Ziziphus genus, metabolomics utilizes LC-MS, GC-MS, and NMR techniques^39,40, coupled with statistical analysis, to uncover metabolic information. This approach is poised to reveal relationships between metabolite composition and various traits, including morphology, diversity, and activity. Despite its promise, there is a notable absence of similar studies in existing databases, making this review a novel contribution to the field.

METHODS:

The investigation methods in this review align with previous meta-analyses on health topics, adhering to precise analytical guidelines in therapeutic and well-being sciences^41-44. Library data were sourced from Google Scholar, Pubmed, and Scopus databases, using specific keywords such as "metabolomic," "metabolites profiling," and "Ziziphus." Literature selection followed the PICO method, initially targeting 100 relevant documents from scientific journals. Papers were screened based on relevance to metabolomics studies on the genus Ziziphus, evaluating titles, abstracts, and content. Details of the search method and results are provided in Table 1.

The study's relevance was determined following the inclusion criteria outlined in Table 2. The analysis needed to meet specific criteria related to the population, intervention, comparison, and desired outcome. After removing the duplicate entries from the search results, a two-stage screening process was conducted. This process encompassed assessing study titles, abstracts, and full content. Predefined questions aligned with the PICO strategy were used during the screening stages to determine which publications fit the review's scope.

Table 1. Literature Search record

No	Database	Population Search Terms	Intervention Search Terms	Search Result
1	Google Scholar	“metabolomic” OR “metabolite profiling.”	“Ziziphus”	100
2	Pubmed	“Metabolomic”	“Ziziphus”	31
3	Scopus	“Metabolomic”	“Ziziphus”	12

Table 2. List of questions utilized for incorporation and avoidance studies during the combined title, abstract, and complete content screenings.

Screenings Stages

Questions

Screening Outcomes

Title and abstract screening

· Does the ponder center on metabolomics?

· Does the study offer an evaluation of the Ziziphus Genus?

Studies are included in case they fulfill all questions

Full-text screening

· Does the study method use chemical analytic tools?

· Does the study present a metabolomics profile from the Species of the Ziziphus Genus?

· Does the study contain a bioassay test?

· Does the study use multivariate analysis to interpret the data?

· Does the study confirm a natural product that is responsible for the activity in the test?

Considers are included on the off chance that they fulfill at slightest two screening questions

RESULTS AND DISCUSSIONS:

From the literature databases, 143 articles were screened, resulting in the selection of 16 reports meeting analysis criteria, as shown in the PRISMA chart (Figure 1). These reports were categorized by year, species, analytical tools used, and research findings on metabolomics profiles and activity tests, detailed in Table 3.

Sixteen articles focusing on metabolomics applications in the Ziziphus genus were gathered (refer to Table 4). However, the data distribution varied due to diverse analytical techniques employed. Some articles compared two or three species within the genus, while others conducted multiple bioassay tests in a single study. Data from each source were extracted and summarized, cataloging metabolite content, multivariate analysis outcomes, and observed bioactivity from bioassay tests. The summarized data is presented in Table 4.

Figure 1. The PRISMA diagram illustrates the collection process of acceptable studies.

Table 3. Data distribution from the collected articles

No	Categorize		Number of Publication
1	Year	2013	1
		2015	1
		2017	1
		2019	1
		2020	2
		2021	4
		2022	6
2	Species	Z. spina-christi	1
		Z. mauritiana	2
		Z. jujuba	14
		Z. lotus	1
		Z. joazeiro	1
3	Analysis Methods	¹H-NMR	2
		GC-MS	2
		LC-MS	18
4	Bioassay or Bioactivity Study Methods	Antioxidant	2
		Tyrosinase Inhibitor	1
		Anti-inflammatory	1
		Anti-hyperglycemic	1
		Restrains Adipogenesis	1
		Antifungal	1

Based on the compiled data, Z. jujuba is the most studied species in the Ziziphus genus using metabolomics since 2013. Metabolomics reveals metabolite profiles based on factors like geographical origin^36,45 ripening stage^46-49, and species^15,50. It identifies primary and secondary metabolites influencing morphology and maturity, especially in fruits⁵¹. Some studies link metabolomics^46,50,52 with bioactivities like antioxidant and anti-inflammatory effects^33,36,50. However, specific metabolites responsible for these activities remain unidentified.

Two articles conducted comparative studies between species^15,50 focusing on metabolomics profiles and activities of seeds and leaves from Z. jujuba, Z. mauritiana, and Z. spina-christi. One study found a close association between Z. spina-christi and Z. mauritiana, indicating their similarity but significant differences from Z. jujuba⁵⁰, as shown by distinct clusters in multivariate analysis of metabolomics profiles. These differences were correlated with variations in antioxidant, anti-inflammatory, and antidiabetic activities observed in vitro. However, statistical analysis did not directly connect metabolomics profiles with activity; instead, hypotheses were drawn from related studies and literature. Notably, this review found no articles statistically linking metabolomics data from the Ziziphus genus to its pharmacological activity.

Metabolomics Studies of Ziziphus based on Species Differences:

In 2019, Sakna et al. conducted a comprehensive metabolomic study on various Ziziphus species, analyzing leaf samples from Z. jujuba, Z. mauritiana, and Z. spina-christi using UHPLC/PDA/ESI-MS. They identified 102 metabolites and found that Z. spina-christi and Z. mauritiana were closely related, distinct from Z. jujuba. Notably, Quercetin-3-O-(2-pentosyl)-rhamnoside distinguished Z. jujuba, while Saponin 54, Saponin 58, and Christinin A were abundant in Z. mauritiana, and Saponin 72 prevailed in Z. spina-christi. Z. spina-christi leaves exhibited superior antioxidant potential and alpha-glucosidase inhibition, while Z. mauritiana leaves showed the most effective COX-1 enzyme inhibition⁵⁰. Another study focused on the seeds of Z. jujuba and Z. mauritiana¹⁵, revealing rich saponins, polyunsaturated fatty acids, and certain amino acids in Z. jujuba seeds, while Z. mauritiana seeds were abundant in saturated fatty acids and flavonoids.

In other studies, Z. spina-christi's leaves, fruits, seeds, and roots demonstrated strong anti-inflammatory activity in animal models^2,30,53,54, with christinin-A and saponin glycosides contributing to glucose level reduction in diabetic animals. The butanol extracts of Z. spina-christi and Christinin-A exhibited similar effects to glibenclamide in improving glycemic control in diabetic rats^55-57. Additionally, studies on Z. mauritiana revealed strong anti-inflammatory properties in its leaves, fruits, seeds, and bark, closely associated with antioxidant and antibacterial activities ^58-60. Molecular docking studies suggest rutin's role in inhibiting proinflammatory cytokine production and modulating the arachidonic acid pathway, including COX, LOX, and phospholipase A2⁶¹.

Some phenolic and flavonoid compounds found in Z. jujuba, Z. mauritiana, and Z. spina-christi include rutin, quercetin, catechin, and gallic acid^2,35,62-64. Rutin has various mechanisms for its antihyperglycemic effect, including reducing carbohydrate absorption in the small intestine⁶⁵, blocking gluconeogenic tissue activity⁶⁶, promoting tissue glucose intake⁶⁷, enhancing insulin release, and protecting pancreatic islets^68,69. Additionally, rutin reduces the formation of sorbitol, oxygen-reactive molecules, AGE precursors, and inflammation mediators⁶⁹. Quercetin decreases glucose, triglycerides, and cholesterol levels, stimulates hexokinase and glucokinase, and protects pancreatic beta cells. Administration of quercetin to rats with STZ-induced diabetes reduces liver enzymes, lipid peroxidation, and promotes antioxidant enzyme function ^70,71. Catechins inhibit alpha-glucosidase activity, reducing maltose-induced blood sugar levels in rats^72,73. Molecular docking investigations suggest that the benzene-ring-4′-hydroxyphenyl structure on flavan-3-ol is significant for inhibiting AGH^74,75 with both catechin and epicatechin hindering glucose absorption in vitro and reducing postprandial glucose levels in vivo⁷⁶. Gallic acid inhibits α-amylase and α-glucosidase activities and FeSO4-induced oxidative stress, showing promise for controlling hyperglycemia and related complications such as myocardial infarction^77,78.

Table 4. Results of data extraction of metabolomics studies on Ziziphus

Species	Organ	Metabolite Content	Multivariate Analysis Results	Bioactivities	Ref
Z. spina-christi	Leaf	Naringenin-6,8-di-C-hexoside, myricetin-3-O-(6-rhamnosyl)-hexoside, quercetin-3-O-(2,6-dirhamnosyl)-hexoside, quercetin-3-O-[(2-hexosyl)-6-rhamnosyl]-hexoside, (epi)cathecin-di-C-hexoside, kaempferol-3-O-(2,6-dirhamnosyl)-hexoside, quercetin-3-O-robinoside, quercetin-3-O-rutinoside, bayarin, quercetin-3-O-hexoside, 3’,5’-di-C-glucopyranosylphloretin, kaempferol-3-O-rutinoside, quercetin-3-O-(2-pentosyl-rhamnoside)-4’-O-rhamnoside, quercetin-3-O-p-coumaroyl (2,6-dirhamnosyl)-hexoside, 6’”-caffeoyl 3’,5’-di-C-glucopyranosylphloretin, quercetin-3-O-(4-O-p-coumaroyl)-2-rhamnosyl-[6-rhamnosyl]-galactoside, kaempferol-3-O-(4-O-p-coumaroyl)-2-rhamnosyl-[6-rhamnosyl]-galactoside, quercetin-3-O--(4-O-p-coumaroyl)-2-rhamnosyl-[6-rhamnosyl]-glucoside, mauritine F, sanjoinine F, kaempferol-3-O--(4-O-p-coumaroyl)-2-rhamnosyl-[6-rhamnosyl]-glucoside, 4(13)-nummularine-C alkaloid, sanjoinine B, oxyphilline A, lotusanine A/frangulofoline, trihydroxy-octadecadienoic acid, jujubogenin-3-O-(di-deoxyhexosyl)-hexsoide, jubanine C, dihydroxy dodecadienoic acid, adouetine Z, trihydroxy-octadecadienoic acid, scutianine A, christinin A/C, 15-acetoxy lotoside IV, christinin B, christinin A2, jujubasaponin II/III isomer, amino-hexadecanediol, heptadecanetriol, oleanonic acid/betulonic acid, caenothic acid, 2-amino-1,3-octadecanediol, hydroxy octadecatrienoic acid, octadecatrienoic acid, maslinic acid, zizyberanalic acid, ceanothic acid isomer, 3-O-Z-p-coumaroylalphitolic acid, 3-O-E-p-coumaroylalphitolic acid, glycerol 1,2-dialkanoates-3-O-hexoside	The HCA dendrogram showed the formation of two clusters, namely Z. jujuba separated from Z. spina-christi and Z. mauritiana. PCA shows Z. jujuba contains quercetin-3-O-(2-pentosyl)-rhamnoside. Christinin A2, christinin A/C, and jubogenin-3-O-(di-deoxyhexosyl)-hexoside overwhelmed the separating metabolites in both Z. spina-christi and Z. mauritiana.	Antioxidant capacity: DPPH 99.37+0.69; ABTS 192.08+7.94; and FRAP 203.24+22.66 mg TE/ g extract. Antihyperglicemic (α-glucosidase inhibition) 27.47+2.30 mg ACAE/g extract. Anti-inflammatory (COX-1 inhibition) 89.31+0.004% at 10 mg/mL.	50
Z. mauritiana	Leaf	Naringenin-6,8-di-C-hexoside, coumaroylquinic acid, myricetin-3-O-(6-rhamnosyl)-hexoside, quercetin-3-O-(2,6-dirhamnosyl)-hexoside, quercetin-3-O-[(2-hexosyl)-6-rhamnosyl]-hexoside, quercetin-3-O-robinoside, quercetin-3-O-rutinoside, quercetin-3-O-hexoside, 3’,5’-di-C-glucopyranosylphloretin, quercetin 3-O-[4-carboxy-3-hydroxy-3-methylbutanoyl]-(→6)-hexoside, quercetin-3-4’-O-dirhamnoside, quercetin-3-O-rhamnoside, di-O-caffeoylcuinic acid, kaempferol-3-O-rhamnoside, 4(14)-amphibine F alkaloid, lotoside III, N-desmethyl hysoducanine A, hysodricanine A, jujubogenin-3-O-(di-deoxyhexosyl)-hexoside, jubanine C, trihydroxy-octadecenoic acid, christinin A/C, 15-acetoxy lotoside IV, christinin A2, ceanothic acid, hydroxy octadecatrienoid acid, maslinic acid, zizyberanalic acid, ceanothic acid isomer, 3-O-Z-p-coumaroylalphytolic acid, betulinic acid,	The HCA dendrogram showed the formation of two clusters, namely Z. jujuba separated from Z. mauritiana and Z. spina-christi. PCA showed Z. jujuba contained quercetin-3-O-(2-pentosyl)-rhamnoside. Christinin A2, christinin A/C, and jujubogenin-3-O-(di-deoxyhexosyl)-hexoside ruled the separating metabolites in both Z. spina-christi and Z. mauritiana.	Antioxidant capacity: DPPH 92.92+2.52; ABTS 176.70+4.85; and FRAP 175.20+12.92 mg TE/ g extract. Antihyperglycemic (α-glucosidase inhibition) 24.65+1.97 mg ACAE/g extract. Anti-inflammatory (COX-1 inhibition) 90.34+4% at 10 mg/mL.	50
	Seed	Spinosin, 6’”-feruloyc spinosyn, Betulinic acid. The content of free amino acids was Ornithine, Arginine, Histidine, Glutamic acid, Asparagine, Serine, Glutamine, Lysine, Alanine, Threonine, Gamma-aminobutyric acid, Proline, Valine, Tyrosine, Isoleucine, Leucine, Methionine, Phenylalanine, and Tryptophan. The content of nucleosides and nucleobases were Guanosine-5’-monophosphate, Inosine, Adenosine, Hypoxanthine, Uridine, and Adenine. The content of fatty acids was Linoleic acid, Linolenic acid, Oleinic acid, Palmitic acid, Stearic acid, TSFA, TMUFA, TPUFA, and TFA.	PCA and OPLS-DA score plots appeared a clear separation between Z. mauritiana and Z. jujuba seeds.	-	15
Z. jujuba	Leaf	Naringenin-6,8-di-C-hexoside, syringoylquinic acid, trimethoxybenzoyl-quinic acid, quercetin-3-O-robinoside, quercetin-3-O-rutiboside, quercetin-2-O-hexoside, kaempferol-3-O-robinoside, kaempferol-3-O-rutinoside, quercetin-3-O-(2-pentosyl)-rhamnoside, N-desmethylsativanine A, sativanine A, daechuines S5, hovenine A, frangulanine, jujubasaponin I, caenothic acid trihexoside, jujubasaponin II/III, jujubasaponin IV/V, jujubasaponin I Isomer, ziziphin, amino hexadecanediol, heptadecanetriol, ceanothetric acid methyl ester, trihydroxy-urs-12-en-28-oic acid, trihydroxy-urs-12-en-28-oic acid isomer, ceanothic acid, ceanothic acid isomer, corosolic acid, pomonic acid, 3-O-E-p-coumaroylalphitolic acid, betulinic acid, methyl ceanothate, glutamine, alanine, threonine, valine, alpha glucose, beta glucose, fructose, sucrose, acetic acid, formic acid, fumaric acid, succinic acid, apigenin, kaempferol, quercetin, rutin, choline, and gamma-amino-butyrate	The HCA dendrogram showed the formation of two clusters, namely Z. jujuba separated from Z. mauritiana and Z. spina-christi. PCA showed Z. jujuba contained quercetin-3-O-(2-pentosyl)-rhamnoside. Christinin A2, christinin A/C, and jujubogenin-3-O-(di-deoxyhexosyl)-hexoside ruled the separating metabolites in both Z. spina-christi and Z. mauritiana. The primary differentially accumulated metabolites (DAMs) were found to be flavonoids, and the leaf coloration was determined by the presence of anthocyanins, which were collected in a manner influenced by light exposure.	Antioxidant capacity: DPPH 35.02+5.51; ABTS 103.67+13.76; and FRAP 100.57+2.62 mg TE/ g extract. Antihyperglycemic(α-glucosidase inhibition) 5.99+1.62 mg ACAE/g extract. The Ziziphus jujuba leaf extract exhibited a significant anti-inflammatory effect with a 76.87+0.13% inhibition of COX-1 at 10 mg/mL. Additionally, the extract showed the ability to suppress adipogenesis in human adipocytes. Docking simulations indicated that apigenin, betulinic acid, maslinic acid, and the Ziziphus jujuba leaf extract exhibited the highest affinity towards PI3K and PPARγ.	46,50,52
	Fruits	More than 400 metabolites were identified in fruit samples, with changes observed in anthocyanin and flavonoid levels during jujube fruit development. Out of the 463 identified metabolites, 29 categories were recognized, with amino acids, lipids, alkaloids, and flavonoids being the most abundant nutrients in dried jujube fruits across seven producing zones in China. In NMR profiling analysis, concentrations of 11 metabolites including Acetate, Alanine, Asparagine, Choline, Creatine, Formate, Glucose, Isoleucine, Sucrose, Threonine, and Valine were quantified.	The PCA and OPLS-DA analysis revealed distinct metabolomic profiles among samples from different stages, indicating clear contrasts in metabolite compositions. Based on the main nutrient content, primary jujube production can be categorized into two regions: the east and west regions in North China. Chlorophyll, Lutein, Delphinidin, and Cyanidin were investigated as pigment-related metabolites in Sianbianhong varieties. Immature jujube exhibits higher concentrations of alanine, formate, and sucrose. By employing WGCNA and examining gene-metabolite relationships, specific modules and transcription factors (ZjHAP3, ZjTCP14, and ZjMYB78) were found to be closely associated with sugar and acid components.		45,47,48,79–83
	Seeds	The metabolites detected by UPLC-MS/MS include various acids and derivatives such as alphirolic acid, glucosylphloretin, ceanothic acid, flavanones, jujubosides, kaempferol rutinoside, and others. Volatile compounds identified via GC-MS encompass fatty acids, alcohols, esters, and glycerol derivatives. Free amino acids present consist of alanine, arginine, glutamine, and others, while nucleosides and nucleobases include guanosine-5’-monophosphate, inosine, and adenine. Fatty acid substances comprise linoleic acid, oleic acid, and others. Additionally, various catechins, glycosides, peptides, saponins, triterpenes, and fatty acids were detected.	Based on the loading plot, ceanothic acid, and jujuboside B were critical components in the second quadrant. In contrast, glycerol ester, linoleic acid derivative, and pseudolaroside B were prominent in the third quadrant. Kaempferol 3-rutinoside and linoleic acid were significant components in the fourth quadrant, contributing to the differentiation between Z. jujuba seeds. The PCA and OPLS-DA score plots demonstrated a distinct separation between Z. jujuba and Z. mauritiana seeds..	-	13,15,84
Z. lotus	Stem Bark	Seven catechins, 2 Clavonol glycosides, 1 Lignan, 10 Cyclopeptides, 17 Saponins, 1 triterpene, and 2 Fatty acids were detected	-	Total phenolic 271.65+5.60 mg GAE/g extract, Total flavonoid content 188.11+7.48 mg AAE/g, DPPH free radical scavenging 304.02+4.80 mg AAE/g, Metal chelating 39.01+4.30, and FRAP 296.68+1.81 me TE/g	33
Z. joazeiro	Bark and Leaf	In a study employing negative ion mode UPLC-ESI-QTOF-MS, ten flavonoids (catechin, myricetin-O-rutinoside, myricetin-O-hexoside, rutin, quercetin-O-glucoside, quercetin-O-hexoside, isorhamnetin-O-rutinoside, isorhamnetin-O-hexoside, kaempferol-O-(sinapoyl)-sophoroside, kaempferol-3-O-(feruloyl)-sophoroside), four saponins (including diosgenin tetraglycoside and saponin derivatives), one phenolic acid (dihydroxybenzoic acid pentoside), and one nitrogen compound (5-allyl-1-(2,3,4-tris-O-benzoylpentafuranosyl)-2,4(1H,3H)–pyrimidinedione) were identified.	-	When evaluating both extracts against Candida spp., higher inhibitory concentration values were observed compared to fluconazole.	36

Metabolomics Studies of Ziziphus Based on Variation in Maturity Levels:

Metabolomic studies on Z. jujuba fruit across various ripening stages revealed distinct metabolic profiles ^46–49. Utilizing advanced techniques like UPLC-MS/MS, these studies identified numerous metabolites, including carbohydrates, nucleotides, organic acids, lipids, amino acids, and vitamins ⁴⁷. Phenolic and flavonoid compounds like rutin, quercetin, catechin, and gallic acid were also investigated, with findings indicating decreasing levels of phenols and flavonoids as the fruit matures ⁴⁸. Concurrently, compounds such as cyclic adenosine monophosphate (cAMP), glucose, and fructose increased, influencing the fruit's taste profile. In the Sanbianhong cultivar ⁸⁰, specific compounds like luteolin, β-carotene, anthocyanins, and chlorophyll were identified as major contributors to ripening and color changes, shedding light on the intricate metabolic dynamics during fruit maturation ⁸¹.

Furthermore, metabolite differences between ripe and immature Z. jujuba fruit were explored, highlighting variations in compounds like formate, alanine, sucrose, glucose, and valine. Additionally, a study on two Ziziphus varieties, Mazao and Ping'anhuluzao, using LC-MS profiling, unveiled 508 metabolites, including sugars and organic acids. The accumulation pattern of sugars primarily during early fruit development impacted sweetness, while organic acid content increased as fruit ripened. Variations in sugar and acid compound accumulation between the two varieties provided crucial insights into metabolic variations influencing fruit ripening and taste ⁸³.

Metabolomics Studies of Ziziphus Based on Variation in Producing Areas:

Metabolomic analyses have explored geographical variations in Z. jujuba fruit, revealing distinct metabolic profiles across different producing areas. Shi et al. (2022) utilized LC-MS/MS-Metabolomics analysis to identify 463 metabolites from seven producing regions, categorizing the primary production into eastern and western North China regions based on nutrient composition ⁴⁵. These findings provide crucial insights into regional metabolic differences within Z. jujuba fruit, facilitating a deeper understanding of its nutritional diversity and potential applications ^4,5,8,85.

Apart from geographical variations, Z. jujuba fruit is recognized for its multifaceted bioactive properties. It contains polysaccharides with antioxidant potential, contributing to its nutritional value and suitability for functional food development. Additionally, the fruit's antioxidant-rich composition, including flavonoids and triterpenoid acids, underscores its health-promoting attributes. Studies have also identified specific compounds within Z. jujuba, such as condensed tannins and spinosin, demonstrating inhibition of enzymes like tyrosinase, highlighting its potential in skincare and pharmaceutical applications ^6,86. Furthermore, Z. jujuba exhibits anti-inflammatory effects attributed to compounds like ursonic acid and ceanothic acid, emphasizing its therapeutic potential in mitigating inflammation-related conditions^49,87,88. Similarly, metabolomic investigations into other Ziziphus species, like Z. joazeiro ³⁶ and Z. lotus, have unveiled diverse bioactive compounds with antioxidant and antifungal properties³⁶, offering prospects for medical and pharmaceutical applications³³.

CONCLUSION:

Metabolomics studies on Ziziphus species, particularly focusing on Z. jujuba fruit, have provided valuable insights into metabolite changes during fruit maturation stages and distinguished profiles between related species. These analyses have implications for various fields such as agriculture, phytochemistry, and pharmaceutical biology. Despite advancements, studies linking metabolite profiles directly to pharmacological activity are limited, with most connections being theoretical based on literature reviews. However, the potential for applying "pharmaco-metabolomics" in pharmacology to identify active ingredients from natural products with pharmacological effects is promising and warrants further exploration and development.

Authorship Contributor Statement:

Ihsanul hafiz: Methodology, Investigation, Data curation, Writing an original draft. Nizar Happyana: Conceptualization, Review, editing, Supervision, visualization. Muhamad Insanu: Conceptualization, Supervision, Data curation, Review, Revising, Illustration.

Declare of Competing Interest:

The authors assert that they have taken all necessary measures to ensure that their work remains free from any potential financial conflicts of interest or personal relationships that could have influenced the findings presented in this article.

ACKNOWLEDGMENT:

We thank the Education Financing Service Center (PUSLAPDIK), The Ministry of Education, Culture, Research, and Technology (KEMENDIKBUDRISTEK), and the Educational Fund Management Institution (LPDP).

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Received on 20.02.2024 Revised on 13.06.2024

Accepted on 07.10.2024 Published on 27.03.2025

Available online from March 27, 2025

Research J. Pharmacy and Technology. 2025;18(3):1446-1455.

DOI: 10.52711/0974-360X.2025.00208

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