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Jujube - Zizyphus lotus

Zizyphus lotus (L.) Lam. is a deciduous shrub belonging to the Rhamnaceae family. It is commonly known as jujube, wild jujube, lotus jujube, African jujube, or Sidra in Arabic-speaking regions. It should not be confused with Ziziphus jujuba Mill. (Chinese jujube or common jujube) or Ziziphus spinosa, which are different species with some overlapping but distinct phytochemical profiles and traditional uses.

Image source and license: https://commons.wikimedia.org/wiki/File:Ziziphus_jujuba_in_Siwa_Oasis_01.jpg.
Modified by Peter Jorgensen.

Botanical and Common Names

Zizyphus lotus (L.) Lam. is known by several common names across different regions:

• Lotus jujube
• African jujube
• Wild jujube
• Sidra (Arabic)
• N'beg (North Africa)
• Hanneb (Tunisia)

It is important to note that Zizyphus lotus is frequently confused with other Ziziphus species, particularly:

• Ziziphus jujuba Mill. (Chinese jujube, common jujube, red date)
• Ziziphus spinosa (Sour jujube, Chinese wild jujube)
• Ziziphus mauritiana (Indian jujube, ber)

Active Compounds

The therapeutic properties of Zizyphus lotus are attributed to various bioactive compounds, including:

• Flavonoids (quercetin, rutin, apigenin)
• Alkaloids (lotusine, lysicamine)
• Saponins (jujubosides)
• Triterpenes (betulinic acid, oleanolic acid)
• Phenolic acids (chlorogenic acid, caffeic acid)
• Cyclopeptide alkaloids (lotusanine, spinanine-A)
• Polysaccharides

Evidence-Based Health Benefits

Research on Zizyphus lotus has revealed numerous potential therapeutic applications, though many studies are preliminary and conducted in vitro or in animal models. Recent systematic reviews and meta-analyses have begun to consolidate this evidence.

• Antioxidant activity: Strong free radical scavenging properties have been consistently demonstrated in multiple studies.
• Anti-inflammatory effects: Reduction of pro-inflammatory markers and inflammation-related pathways.
• Anxiolytic and sedative properties: Particularly associated with the seed extracts.
• Antidiabetic activity: Blood glucose lowering effects and protection of pancreatic β-cells.
• Hepatoprotective effects: Protection against liver injury and reduction of liver enzymes.
• Antimicrobial activity: Effective against various bacterial and fungal strains.
• Anticancer potential: Cytotoxic activity against several cancer cell lines, although evidence is preliminary.
• Gastroprotective effects: Protection against gastric ulcers.
• Neuroprotective activity: Potential benefits for neurodegenerative disorders.

Recommended Dosages

Standardized dosing guidelines for Zizyphus lotus are limited due to insufficient clinical trials. Based on the available literature:

• Leaf extracts: 250-500 mg daily (standardized to contain at least 2% flavonoids)
• Root bark: 1-2 g of dried powder or 200-400 mg of extract (standardized to contain minimum 1.5% cyclopeptide alkaloids)
• Fruit: 3-6 g of dried fruit or 1-2 g of extract daily
• Seed extracts: 100-300 mg (standardized to contain minimum 2% jujubosides for anxiolytic effects)

It is important to note that these dosages are derived from limited studies and traditional use rather than comprehensive clinical trials. Most studies use extracts with different standardization methods, making direct comparisons challenging.

Side Effects and Safety Profile

Zizyphus lotus is generally considered safe when consumed in traditional food amounts or at recommended supplemental doses. However, reported adverse effects include:

• Mild gastrointestinal disturbances (stomach upset, diarrhea)
• Drowsiness and fatigue (particularly with seed extracts)
• Potential hypoglycemic effects, requiring caution in diabetic patients
• Possible drug interactions with sedatives, antidiabetic medications, and immunomodulatory drugs
• Not recommended during pregnancy and lactation due to insufficient safety data

High-Dose Studies and Knowledge Gaps

Few studies have investigated doses significantly above the therapeutic range. Limited research suggests:

• Doses exceeding 1000 mg/kg in animal models have shown signs of toxicity including hepatic enzyme elevation
• No systematic high-dose studies in humans have been conducted
• The long-term safety profile of high-dose supplementation remains a significant knowledge gap
• The effective therapeutic window for specific conditions is not well established
• Dose-dependent relationships for most therapeutic effects require further investigation

The maximum effective dose appears to plateau for most benefits, with higher doses potentially increasing risk of side effects without proportional therapeutic advantages. However, this represents a major knowledge gap requiring further research.

Research Limitations and Future Directions

Current research on Zizyphus lotus faces several limitations:

• Lack of large-scale clinical trials
• Inconsistent standardization of extracts across studies
• Limited bioavailability and pharmacokinetic data
• Inadequate investigation of potential drug interactions
• Insufficient toxicology studies for long-term use
• Need for comparative studies between different Ziziphus species

References

Alsayari, A., & Wahab, S. (2021). Genus Ziziphus for the treatment of chronic inflammatory diseases. Saudi Journal of Biological Sciences, 28(12), 6897-6914.

Bencheikh, N., Bouhrim, M., Merrouni, I. A., Boutahiri, S., Kharchoufa, L., Addi, M., ... & Elachouri, M. (2021). Antihyperlipidemic and antioxidant activities of flavonoid-rich extract of Ziziphus lotus (L.) lam. fruits. Applied Sciences, 11(17), 7788.

Bencheikh, N., Radi, F. Z., Fakchich, J., Elbouzidi, A., Ouahhoud, S., Ouasti, M., ... & Elachouri, M. (2023). Ethnobotanical, phytochemical, toxicological, and pharmacological properties of Ziziphus lotus (L.) lam.: a comprehensive review. Pharmaceuticals, 16(4), 575.

Hammi, K. M., Essid, R., Khadraoui, N., Ksouri, R., Majdoub, H., & Tabbene, O. (2022). Antimicrobial, antioxidant and antileishmanial activities of Ziziphus lotus leaves. Archives of Microbiology, 204(1), 119.

Ruan, J., Li, H., Lu, M., Hao, M., Sun, F., Yu, H., ... & Wang, T. (2023). Bioactive triterpenes of jujube in the prevention of colorectal cancer and their molecular mechanism research. Phytomedicine, 110, 154639.

Sakna, S. T., Maghraby, Y. R., Abdelfattah, M. S., & Farag, M. A. (2023). Phytochemical diversity and pharmacological effects of triterpenes from genus Ziziphus: A comprehensive review. Phytochemistry Reviews, 22(6), 1611-1636.

Zazouli, S., Chigr, M., Ramos, P. A., Rosa, D., Castro, M. M., Jouaiti, A., ... & Silvestre, A. J. (2022). Chemical profile of lipophilic fractions of different parts of Zizyphus lotus L. by GC-MS and evaluation of their antiproliferative and antibacterial activities. Molecules, 27(2), 483.