Gardenia Jasminoides: A Comprehensive Reference
1. Identity and Botanical Classification
1.1 Taxonomy and Nomenclature
Gardenia jasminoides Ellis is a popular shrub in the Rubiaceae family. Also known as "Cape Jasmine," it is an East Asian blooming species indigenous to East Asia. It is also commonly named gardenia, cape jasmine, or cape jessamine, and is a popular evergreen shrub. In traditional Chinese medicine, the plant is known by the name Zhizi (栀子), while its dried ripe fruit is referred to pharmaceutically as Gardeniae Fructus. The species is a member of the Rubiaceae (coffee) family.
G. jasminoides is distributed in the tropical and subtropical regions of the world, especially in south of the Yangtze River of China. The fruit is harvested when mature and dried, developing its characteristic deep yellow-orange color. The fruit is an ovoid, yellow or yellow-orange berry containing slightly bent seeds.
1.2 Plant Parts Used and Common Preparations
Gardenia fruit (GF) is the mature fruit of Gardenia jasminoides Ellis, boasting a rich array of nutrients and phytochemicals. Over time, GF has been extensively utilized in both food and medicinal contexts. Gardenia fruit, roots, leaves, seeds, and blossoms can all be used medicinally.
Gardenia flowers can be eaten raw, pickled, or preserved in honey. In China, the petals are used in tea for their aroma, while a yellow-red dye used in textiles and sweets has been extracted from the pulp of the fruit. Industrial applications for GF include utilizing gardenia yellow/red/blue pigments in the food industry and incorporating it with other herbs in traditional Chinese medicine.
Common preparation forms include: dried whole fruit (for decoction), standardized aqueous or ethanolic extracts of the fruit, isolated constituent preparations (especially geniposide and crocin), and the plant's pigments as food colorants. Gardenia yellow pigment has been the most important source of a natural colorant for food, cloth, and paint for thousands of years.
2. Traditional and Historical Use
2.1 Traditional Chinese Medicine (TCM)
Its dried fruits, used as a traditional herbal medicine, were first recorded in the book named Shennong Ben Cao Jing (the Classic of Herbal Medicine in China). Zhi Zi (the TCM name for Gardenia jasminoides fruit) has been recorded in Chinese medical texts for over two thousand years and appears in classical formulas such as Zhi Zi Chi Tang, traditionally used to address irritability and restlessness caused by heat.
Zhi Zi (Gardenia jasminoides), commonly known as Gardenia Fruit, is a widely used heat-clearing herb in Traditional Chinese Medicine (TCM). For centuries, it has been valued for its ability to drain fire, eliminate irritability, clear heat, and cool the blood. In classical Chinese herbal medicine, Zhi Zi is frequently included in formulas designed to clear heat from the heart, liver, and lungs, relieve restlessness, and eliminate toxic heat from the body.
Called zhi-zi in traditional Chinese medicine, it was a folk remedy for jaundice, oedema, and fevers. It is classified as a "Middle grade" drug and is recorded in the Chinese pharmacopoeia with various effects, such as eliminating vexation, reducing fever, and cooling blood.
The herb has also been processed in China according to the record in the Treatise on Febrile Diseases and it is considered a medicine-food homology by the National Health Commission of the People's Republic of China. The Ministry of Health has listed it as one of the first pharmaceutical or food resources.
YCHT (Yin-Chen-Hao-Tang) is an aqueous extract derived from three herbs: Artemisia capillaries Thunb (Herba Artemisiae Capillaris, Yin-Cen-Hao), Gardenia jasminoides Ellis (Fructus Gardeniae, Zhi-zi) and Rheum officinale Baill (Emodin, Da-huang), with a ratio of 4:3:1 in weight. Yin-Chen-Hao-Tang decoctions have long been used as anti-inflammatory, antipyretic, choleretic, and diuretic agents for liver disorders and jaundice.
2.2 Use in Japan and Korea
In addition to its use in traditional Chinese medicine, G. jasminoides has been widely used in folk medicine in Japan and Korea for hundreds of years to treat fever, gastrointestinal issues, and inflammation. Shishihakuhito is a Chinese herbal medicine mainly composed of gardenia fruit and is used to treat atopic dermatitis.
2.3 Traditional Preparations and Purposes
In ethnic, traditional, and folk medicine, GJE has been used to treat fever and cold and relieve nervous anxiety. Gardenia jasminoides is used in traditional Chinese medicine for various properties, including emollients, emetics, diuretics, vermifuge, antispasmodics, antiseptics, and analgesics. The dried fruit and fresh blossoms and leaves have traditionally been made into tea used to calm nerves, treat diabetes, and help with sleep.
3. Key Constituents and Active Compounds
3.1 Overview of Phytochemical Composition
Approximately 162 compounds have been isolated and identified from this medicinal plant. Iridoid glycosides and yellow pigment are generally considered the main bioactive and characteristic ingredients, and geniposide is used as an indicator. An examination uncovers a variety of bioactive phytoconstituents, such as flavonoids, iridoid glycosides, gardenia's yellow pigment, monoterpenoids, sesquiterpenoids, triterpenoids, organic acids and their derivatives, along with other compounds.
A number of chemical components of G. jasminoides have been isolated and characterized, including iridoids, iridoid glucosides, triterpenoids, organic acids, and volatile compounds. Geniposide, genipin, gardenoside, crocin, and iridoids are the major bioactive compounds found in G. jasminoides. The major volatile compounds in essential oil of G. jasminoides are aliphatic acids, ketones, aldehydes, esters, alcohols, and aromatic derivatives.
3.2 Geniposide and Genipin
Geniposide (C17H24O10), a well-known iridoid glycoside compound, is one of the main bioactive components of traditional Chinese medicine Gardeniae Fructus, the dried ripe fruit of Gardenia jasminoides Ellis (Zhizi in Chinese). This compound is also considered as a glycoside consisting of one molecule of genipin and one molecule of glucose.
Genipin reduces insulin resistance, demonstrates antidepressive and antithrombotic effects, provides protection against liver damage, and inhibits gastric lesions. The active mechanisms are related to enhancement of SOD, GSH, CAT, IDE, PPARγ, and FoxO1, inhibition of ROS, NO, ALT, AST, and α-synuclein, and regulation of signaling pathways such as AMPK, NF-κB, and PI3K/Akt.
After oral administration of genipin and geniposide, genipin sulfate was a major metabolite in the bloodstream, whereas the parent forms of genipin and geniposide were not detected.
Regarding concentration in the fruit: The geniposide content in G. jasminoides fruit showed a trend of decrease from 60 days after flowering (DAF) to 120 DAF, then remained steady during the fruit ripening stages. The highest concentration was 2.035 ± 0.004% in the early stage at 60 DAF when the fruit was young and bluish green.
3.3 Crocins and Crocetin
Crocin — a water-soluble carotenoid — is found in the fruits of gardenia (Gardenia jasminoides Ellis) and in the stigmas of saffron (Crocus sativus Linne). Crocin has many medicinal effects such as antioxidant and anti-inflammatory activities, is antihyperlipidemic, and is protective of the injured liver.
Crocin-I content in G. jasminoides fruit showed a continuous increase from 0.519 ± 0.039% in young fruit (60 DAF) to the highest cumulative amount of 1.098 ± 0.020% in matured fruit (180 DAF).
Numerous studies have shown crocins to be capable of a variety of pharmacological effects, such as protection against cardiovascular diseases, inhibition of tumor cell proliferation, neuroprotection, and protection of hepatocytes. Among the mechanisms underlying their various protective actions, the antioxidant activity was hypothesized to be responsible for various pharmacological effects of crocins.
3.4 Gardenoside and Other Iridoids
The principal bioactive and distinguishing components of Gardenia are widely regarded as iridoids (geniposide, genipin) and crocins (crocetin, crocin, crocin II). Shared compounds (crocin, crocin II, geniposide, genipin, and crocetin) have demonstrated significant pro-proliferative effects on LPS-induced RAW 264.7 cells and inhibitory effects on inflammatory factors NO, TNF-α, IL-6, and IL-1β in pharmacological studies.
3.5 Polyphenols, Flavonoids, and Other Constituents
The chemical constituents present in Gardenia plants include triterpenes, carotenoids (e.g., crocins), iridoid glycosides, quinic acid derivatives, amides, and fatty acids. Some preparations have also been found to contain polyphenolic compounds. Additional isolates from the flowers of wild Gardenia jasminoides include iridoids such as coumaroylshanzhiside derivatives and a phenylpropanoid glucoside.
4. Established Mechanisms of Action
4.1 Anti-Inflammatory Mechanisms
Geniposide plays an anti-inflammatory role via regulating TLR4 and downstream signaling pathways in lipopolysaccharide-induced inflammation in mice. Geniposide also suppressed arthritis in adjuvant-induced arthritis rats by decreasing the expression levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, increasing the production of IL-10, and inhibiting the expression of phospho-p38 (p-p38) related proteins.
Gardenia jasminoides is a widely used herbal medicine with anti-inflammatory properties. Investigation of whether 70% ethanolic GJ extract and its subsequent fractions inhibit ORAI1 (a calcium channel important in generating intracellular calcium signaling for T cell activation) revealed that the extract (64.7% ± 3.83% inhibition at 0.1 mg/ml) and all fractions showed inhibitory effects on the ORAI1 channel.
4.2 Antioxidant Mechanisms
Purified crocin with purity of >99.6% has antioxidative activity at concentrations up to 40 ppm. At 20 ppm, the antioxidative activity of crocin is comparable to that of butylated hydroxyanisole (BHA). Geniposide and genipin further contribute to antioxidant activity through enhancement of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) activity while suppressing reactive oxygen species (ROS).
4.3 Neuroprotective Mechanisms
A growing body of evidence shows that the neuroprotective benefit of geniposide probably arises from its agonist action on the glucagon-like peptide-1 receptor (GLP-1R). Geniposide, a bioactive iridoid glycoside isolated from Gardenia jasminoides Ellis, as well as an agonist of Glucagon-like peptide-1 receptor (GLP-1R), has been reported to exhibit antidepressant-like effects in several rodent models.
4.4 Antidiabetic Mechanisms
The hypoglycemic mechanism of α-glucosidase inhibitors works by inhibiting α-glucosidase in the intestinal mucosa, slowing the breakdown of starches into glucose and reducing absorption of glucose in the small intestine. Related studies showed that gardenia can effectively inhibit the activity of α-glucosidase.
Genipin suppressed intracellular lipid accumulation caused by free fatty acid treatment and also significantly increased the intracellular expression of a fatty acid oxidation-related gene (peroxisomal proliferator-activated receptor PPARα). These results confirmed that geniposide has an anti-obesity effect, an insulin resistance-alleviating effect, and an abnormal lipid metabolism-alleviating effect, and the metabolite genipin shows a direct effect on the liver, inducing expression of a lipid metabolism-related gene as one of its molecular mechanisms.
4.5 Hepatoprotective Mechanisms
In animal models, Gardenia jasminoides significantly reduced liver mRNA and/or protein expression of transforming growth factor β1 (TGF-β1), collagen type I (Col I), and α-smooth muscle actin (α-SMA). It significantly suppressed the upregulation of these fibrotic markers in human hepatic stellate cells (LX-2) exposed to recombinant TGF-β1, and inhibited TGF-β1-induced Smad2 phosphorylation in LX-2 cells.
The polysaccharide fraction of G. jasminoides (GPS) also inhibited the Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling, decreased the expression of inflammatory factor genes, and ameliorated hepatic inflammation.
5. Scientific Evidence by Area of Use
5.1 Hepatoprotection and Liver Disease
Preclinical evidence (animal and in vitro): Treatment with Gardenia jasminoides decreased serum alanine aminotransferase (BDL vs BDL + 100 mg/kg Gardenia jasminoides: 146.6 ± 15 U/L vs 77 ± 6.5 U/L, P = 0.0007) and aspartate aminotransferase (188 ± 35.2 U/L vs 128 ± 19 U/L, P = 0.005) as well as hydroxyproline (438 ± 40.2 μg/g vs 228 ± 10.3 μg/g liver tissue, P = 0.004) in bile duct-ligated rats.
In a mouse model of acetaminophen (APAP)-induced liver injury, levels of serum hepatic transaminases and inflammatory markers, including IL-6 and TNF-α, significantly decreased in mice treated with Gardenia jasminoides fruit extract compared to those in the APAP group, with significant improvement in hepatic histology and hepatic GSH levels also observed.
In a cholestatic mouse model, GPS administration dose-dependently ameliorated impaired hepatic function, including a 2–7-fold decrease in aminotransferase levels, upregulated the expression of farnesoid X receptor (FXR) and pregnane X receptor (PXR) and their downstream efflux transporters, and decreased levels of 12 bile acids. Furthermore, GPS ameliorated gut microbiota dysbiosis, improved intestinal barrier function, and reduced serum and hepatic lipopolysaccharide levels 1.5-fold.
A study in a rat model of NASH with fibrosis induced by a high-fat, high-fructose diet investigated the therapeutic potential of GJE. Male Sprague-Dawley rats were assigned to groups including a low-dose GJE group treated with 0.119 g/kg BW of GJE and a high-dose GJE group treated with 0.239 g/kg BW of GJE. Gardenia jasminoides exhibits promising anti-inflammatory and anti-fibrotic properties in this model, suggesting its potential as a therapeutic candidate for NASH-related liver fibrosis.
Evidence strength: Evidence for hepatoprotective effects is primarily preclinical (rodent models and cell culture). There is a notable absence of robust controlled human clinical trials specifically evaluating Gardenia jasminoides fruit extract for liver disease endpoints. Several studies provide clinical evidence of effectiveness of the traditional compound formula YCHT (which includes gardenia) in the treatment of various liver diseases, but isolating the specific contribution of G. jasminoides from such multi-herb preparations in human studies has not been systematically done.
5.2 Anti-Inflammatory Activity
Preclinical evidence: The traditional use of Gardenia jasminoides as an anti-inflammatory agent has been confirmed in mouse models and in vitro. This plant has extensive utility in the history of Traditional Chinese Medicine and is acknowledged for its ability to combat inflammation, safeguard liver health, and possess antioxidant capabilities.
Shishihakuhito, a Chinese herbal medicine mainly composed of gardenia fruit, is used to treat atopic dermatitis, and it inhibits immunoglobulin E (IgE)-mediated histamine release.
Evidence strength: Anti-inflammatory effects have been well-documented in cell culture and animal models. Human clinical evidence specific to isolated Gardenia jasminoides is limited, with most human application occurring via complex multi-herb formulations used in TCM or Kampo traditions.
5.3 Antidiabetic Effects and Metabolic Syndrome
Preclinical evidence: In spontaneously obese Type 2 diabetic mice, geniposide showed suppression of body weight and visceral fat accumulation, alleviation of abnormal lipid metabolism, and suppression of intrahepatic lipid accumulation. In addition, geniposide alleviated abnormal glucose tolerance and hyperinsulinemia, suggesting that geniposide has an insulin resistance-alleviating effect.
In studies evaluating geniposide and crocin I on type 2 diabetes mellitus, geniposide demonstrated the best effect, with the order of hypoglycemic potency ranked as geniposide > crocin I > crude extract of gardenia. Crocin obtained from water extracts of G. jasminoides was found to exhibit antihyperlipidemic effects; when crocin and crocetin were given to tested mice, triglyceride and total cholesterol were significantly decreased.
Evidence strength: Evidence is predominantly from animal and in vitro studies. Clinical data in humans with type 2 diabetes or metabolic syndrome using Gardenia jasminoides preparations is very limited and does not yet allow definitive efficacy conclusions.
5.4 Neuroprotection, Cognitive Function, and Antidepressant Activity
Preclinical evidence: Recent studies have confirmed the significant efficacy of GJE for treating central nervous system (CNS) disorders, including Alzheimer's disease, Parkinson's disease, and major depressive disorder in preclinical settings; however, GJE has not been systematically evaluated in controlled human trials.
In studies using the repeated restraint stress (RRS)-induced depression model in mice, geniposide treatment significantly ameliorated depression-like behaviors induced by RRS, such as decreased sucrose preference, reduced locomotor activity, and extended immobility time in tail suspension and forced swimming tests.
An animal experiment showed that geniposide as a major compound in gardenia fruit could alleviate depression-like behavior in diabetic mice by enhancing brain-derived neurotrophic factor (BDNF) expression. Another research found that oil from GF exhibited anti-depressant effects via protein kinase A, cAMP response element-binding protein, and BDNF signaling.
Evidence strength: Evidence for neuroprotective and antidepressant effects is largely from animal models and mechanistic in vitro studies. Human clinical trial data are absent or very preliminary for these endpoints.
5.5 Sleep Quality
Human clinical evidence: A pilot study investigated the effect of crocetin (derived from Gardenia jasminoides Ellis) on sleep. The clinical trial comprised a double-blind, placebo-controlled, crossover trial of 21 healthy adult men with a mild sleep complaint, including two intervention periods of 2 weeks each, separated by a 2-week washout period. Objective sleep quality was measured using an actigraph, and subjective symptoms were assessed using St Mary's Hospital Sleep Questionnaire. Actigraph data showed that after administration of crocetin, the number of wakening episodes was reduced compared to that of the placebo (p=0.025).
Evidence strength: This is one of the few available human clinical studies. However, it is a small pilot study (n=21) and should be considered preliminary. The study evaluated crocetin specifically, not a whole-plant extract. Larger, more robust trials are needed before clinical conclusions can be drawn.
5.6 Cardiovascular Effects
Numerous studies have confirmed that crocins and iridoid glycosides have effects of antioxidation, anti-inflammatory activity, anti-atherosclerosis, anti-ischemic brain injuries, anti-platelet aggregation, anti-hyperglycemia, anti-hyperlipidemia, and anti-hypertension. From basic pharmacological research of GJE extract on several rat models, GJE extract markedly prolonged bleeding time and inhibited platelet aggregation and thrombosis.
Evidence strength: Cardiovascular evidence is entirely preclinical (animal models and in vitro). No robust human clinical trials have specifically tested Gardenia jasminoides extracts for cardiovascular endpoints.
5.7 Antitumor / Anticancer Activity
Genipin gentiobioside can treat heart failure, while geniposide, crocin 1, and crocin 2 are confirmed to have anti-cancer effects in colon and bladder cancer cell lines. Gardenoside has a demonstrated effect on HepG2 liver cancer cells cultured in vitro. These ingredients can induce cancer cell apoptosis through their influence on the expression of Bcl-2 and other genes, which may be the main mechanism for the anticancer effect.
The fruit of Gardenia jasminoides contains the natural iridoid geniposide, which has anti-inflammatory, antioxidant, anticancer, antidiabetic, hepatoprotective, and immunomodulatory properties.
Evidence strength: Anticancer evidence is exclusively from in vitro cell studies and animal models. There are no human clinical trials demonstrating anticancer efficacy of G. jasminoides preparations in oncology.
5.8 Skin and Dermatological Applications
Gardenia jasminoides extract exhibited antioxidative and antiapoptotic effects in skin cells exposed to UVB radiation. UVB-induced injury and inflammatory responses of skin cells were attenuated by gardenia extract treatment.
Evidence strength: These findings are in vitro. No human clinical trial data are available in these sources to support dermatological use beyond the traditional Kampo application for atopic dermatitis.
6. Body Systems and Associated Health Areas
Various pharmacological properties have been validated, including a beneficial effect on the nervous, cardiovascular, and digestive systems, hepatoprotective activity, antidepressant activity, and anti-inflammatory activity.
- Hepatobiliary system: Hepatoprotection, antifibrotic effects, support for cholestatic conditions, jaundice.
- Central nervous system: Neuroprotective effects relevant to Alzheimer's disease and Parkinson's disease models; antidepressant activity; sedative/sleep-quality effects.
- Cardiovascular system: Anti-atherosclerotic, antithrombotic, antihypertensive, and antihyperlipidemic effects (preclinical).
- Endocrine/Metabolic system: Antidiabetic effects via α-glucosidase inhibition and insulin resistance reduction; anti-obesity effects (preclinical).
- Immune system: Anti-inflammatory, immune-modulatory, anti-atopic dermatitis.
- Digestive system: Gastroprotection, choleretic activity, influence on gut microbiota.
These components are implicated in wide-ranging pharmacological applications, which encompass antioxidant, anti-inflammatory, anti-diabetic, cardiovascular disorders, neurodisorders, anti-tumor, treatment of liver injury, anti-hepatic injury, gastrocellular activity, improvement of gut microbiota, atopic dermatitis, anti-viral, improvement of the quality of sleep, protection from blue light and ultraviolet rays, vitiligo, inhibition of retinal damage, antibacterial activity, anti-senescence activity, anti-thrombosis, osteoporosis protection, and postmenopausal syndrome.
7. Dosage Forms and Reported Study Dosages
The following dosages are those reported in specific studies as cited; they are not recommendations.
- Hepatoprotective animal studies: Doses of 100 mg/kg of Gardenia jasminoides were evaluated in bile duct-ligated rats.
- NASH model animal studies: A low-dose GJE group received 0.119 g/kg body weight and a high-dose group received 0.239 g/kg body weight in a rat model of NASH with fibrosis.
- Crocetin sleep pilot (human): The clinical trial comprised a double-blind, placebo-controlled, crossover trial in 21 healthy adult men, with two intervention periods of 2 weeks each separated by a 2-week washout period. The specific crocetin dose is not detailed in the available excerpts from this source.
- Geniposide toxicology studies (animal): The lethal dose, 50% (LD50), of per oral geniposide was 1431.1 mg/kg. The acute toxicity study indicated geniposide at doses of 574 mg/kg or more could cause hepatic toxicity in rats, with hepatotoxicity often appearing at 24–48 hours after oral administration. A subchronic toxicity study showed geniposide did not cause hepatotoxicity at doses of 24.3 and 72.9 mg/kg orally for 90 days in rats.
- Subchronic tolerance (animal): Geniposide did not exert obvious toxicity in rats upon administration for no more than 13 weeks at doses of ≤100 mg/kg.
- Traditional minimum dose reference: The median dosage of geniposide administered to mice in one study was determined to be 110 mg, based on the recommended minimum dose of 6 g of Gardenia jasminoides Ellis commonly utilized in traditional medicine.
8. Safety Considerations and Notable Adverse Effects
8.1 Dose-Dependent Hepatotoxicity
One of the most significant and well-characterized safety concerns for Gardenia jasminoides is the paradoxical hepatotoxicity of its major active constituent at high doses. Although geniposide has a wide range of biological activities, its toxicity needs to be addressed. Hepatotoxicity is a fundamental issue affecting the safety of geniposide. A study in rats revealed that high doses of geniposide (574 mg/kg or more) cause acute hepatotoxicity after 24–48 hours of oral administration — an effect that may be related to oxidative stress — whereas normal doses of geniposide (24.3 mg/kg or less) do not cause hepatotoxicity, even when repeatedly administered for 90 consecutive days.
The hepatotoxicity was associated with oxidative stress, including decrease of total superoxide dismutase activity and increase of malondialdehyde concentration in rats' livers. In addition to normal rats, rats with α-naphthyl isothiocyanate (ANIT)-induced cholestasis also exhibit hepatotoxicity after geniposide administration, resulting in severe pathological damage to the liver.
Geniposide, a major active constituent of the traditional medicinal herb Gardenia jasminoides ELLIS fruit, exhibits remarkable anti-inflammatory, antiapoptotic, and antifibrotic properties and has been used in a variety of medical fields, mainly for the treatment of liver diseases. However, geniposide-induced hepatotoxicity has been an area of ongoing investigation.
8.2 Intestinal Mechanisms of Toxicity
The intestinal damage caused by geniposide, including necrosis of intestinal epithelial cells and destruction of tight junction structures, precedes liver damage at high doses. Intestinal microbiota-mediated covalent modification of hepatic proteins by genipin dialdehyde may play a crucial role in the liver injury of geniposide, highlighting the contribution of intestinal microbiota to the metabolic activation of this compound.
8.3 Mesenteric Phlebosclerosis
A clinically significant and well-documented adverse effect associated with long-term use of Gardenia jasminoides-containing preparations is idiopathic mesenteric phlebosclerosis (IMP). Many recent reports have suggested a possible association between Japanese traditional (Kampo) medicines containing Gardeniae Fructus (GF) and mesenteric phlebosclerosis (MP). MP is a chronic orphan disease characterized by venous calcification extending from the colonic wall to the mesentery, usually developing in the proximal colon.
Which Chinese herb is the culprit in MP cases is often unclear, but extracts of Gardenia jasminoides have been reported to be responsible. Hiramatsu et al. showed that 70.4% of IMP patients have exposure to sanshishi, which is an extract of Gardenia jasminoides.
While mechanisms are not entirely clear, it is possible that geniposide, the main component of Gardenia jasminoides, may be transferred to genipin, which is absorbed into the mesenteric veins and causes intimal hyperplasia, venous wall thickening, and fibrosis, resulting in "mummification," with subsequent obstruction of venous lumen producing inadequate venous return, intestinal wall thickening, edema, gliosis, and sclerosis, eventually progressing to mesenteric phlebosclerosis.
Clinical research has shown that patients administered a formulation containing Gardenia jasminoides Ellis have exhibited mesenteric venous sclerosis (MP), a chronic ischemic condition marked by mesenteric venous sclerosis of uncertain origin.
8.4 Skin and Organ Pigmentation
It is suggested that genipin, a metabolite of geniposide (the major ingredient of gardenia fruit), is involved in bronze coloration observed with long-term use. A patient who took the extract of gardenia fruit for 7 years developed skin pigmentation complicated with mesenteric phlebosclerosis. In 2020, a case of someone who had developed blue-gray discoloration of the skin as a result of chronic intake of gardenia fruit extract was published.
In long-term animal administration studies, a significant decrease in body weight gain and food consumption occurred in the 2% GF group, and pigmentation of the liver, kidney, and spleen in macroscopic or histopathological examination was observed after 11-month administration, which disappeared after a 3-month recovery period.
8.5 Potential Drug Interactions and Bioavailability Modulation
Herb–herb combinations, such as the combination of Gardenia jasminoides Ellis (ZZ) with Fructus aurantii immaturus (ZS) and/or Cortex magnoliae officinalis (HP), may increase the absorption of geniposide and increase its oral bioavailability. This has implications for potential changes in both therapeutic and toxic effects when G. jasminoides is used as part of traditional herbal formulations.
8.6 Patients with Pre-existing Cholestasis
Rats with α-naphthylisothiocyanate (ANIT)-induced cholestasis exhibit hepatotoxicity after geniposide administration, resulting in severe pathological damage to the liver, suggesting caution is warranted in individuals with pre-existing bile flow impairment.
References
- Chen L, et al. "Gardenia jasminoides Ellis: Ethnopharmacology, phytochemistry, and pharmacological and industrial applications." J Ethnopharmacol. 2020. (PubMed)
- Research and application progress of Gardenia jasminoides – ScienceDirect (2018)
- Gardenia jasminoides Ellis: Ethnopharmacology, phytochemistry, and pharmacological and industrial applications – ScienceDirect (2020)
- Liu H, et al. "Fructus Gardenia phytochemistry, pharmacology of cardiovascular, and safety." J Asian Nat Prod Res. 2013. (PubMed)
- Gardenia fruit: a critical review of its functional nutrients, processing methods and health-promoting effects – PubMed (2023)
- Phytochemical constituents, therapeutic potential and toxicity of Gardenia jasminoides Ellis: An in-depth review – ScienceDirect (2025)
- Chemistry and bioactivity of Gardenia jasminoides – PMC/NIH
- Diverse Pharmacological Activities and Potential Medicinal Benefits of Geniposide – PMC/NIH
- Updated Pharmacological Effects, Molecular Mechanisms, and Therapeutic Potential of Natural Product Geniposide – PMC/NIH
- Diverse Pharmacological Activities and Potential Medicinal Benefits of Geniposide – Evidence-Based Complementary and Alternative Medicine (2019)
- Geniposide improves repeated restraint stress-induced depression-like behavior in mice via GLP-1R/AKT signaling – PubMed (2018)
- Geniposide, from Gardenia jasminoides Ellis, inhibits the inflammatory response in the primary mouse macrophages and mouse models – PubMed
- Gardenia jasminoides attenuates hepatocellular injury and fibrosis in bile duct-ligated rats and human hepatic stellate cells – PMC/NIH
- Gardenia jasminoides extract mitigates acetaminophen-induced liver damage in mice – BMC Complementary Medicine and Therapies (2024)
- Gardenia jasminoides extract mitigates acetaminophen-induced liver damage in mice – PMC/NIH (2024)
- Gardenia jasminoides fruit extract ameliorates NASH with fibrosis by modulating inflammatory and fibrogenic pathways – PLOS One
- Gardenia jasminoides Ellis polysaccharide ameliorates cholestatic liver injury – ScienceDirect (2022)
- Effect of crocetin from Gardenia jasminoides Ellis on sleep: a pilot study – PubMed (2010)
- Effect of crocetin from Gardenia Jasminoides Ellis on sleep: A pilot study – ScienceDirect (2010)
- Effective Therapeutic Verification of Crocin I, Geniposide, and Gardenia on Type 2 Diabetes Mellitus In Vivo and In Vitro – PMC/NIH
- Gardenia fructus antidepressant formula for depression in diabetes patients: A systematic review and meta-analysis – ScienceDirect (2019)
- Antioxidant properties of crocin from Gardenia jasminoides Ellis – PubMed
- HPLC-Analysis of Polyphenolic Compounds in Gardenia jasminoides and Determination of Antioxidant Activity – PMC/NIH
- Potential hepatotoxicity of geniposide, the major iridoid glycoside in dried ripe fruits of Gardenia jasminoides (Zhi-zi) – ResearchGate
- Proteomic Investigation of Signatures for Geniposide-Induced Hepatotoxicity – Journal of Proteome Research (ACS)
- A potential herbal component for the future treatment of fatty liver disease: Geniposide from gardenia – PMC/NIH
- Geniposide dosage and administration time: Balancing therapeutic benefits and adverse reactions in liver disease treatment – ScienceDirect (2024)
- Geniposide Causes Idiopathic Mesenteric Phlebosclerosis – PMC/NIH
- Effects of Long-Term Administration of Gardeniae Fructus on Intra-Abdominal Organs of Rats – PMC/NIH (2020)
- Gardenia Fruit–Related Blue-Gray Skin Pigmentation – ResearchGate (2020)
- Clinical challenges in diagnosing idiopathic mesenteric phlebosclerotic colitis – Frontiers in Gastroenterology (2025)
- Gardenia jasminoides extract and its constituent, genipin, inhibit activation of CD4+ T cells via ORAI1 channel – PMC/NIH
- Gardenia jasminoides – Wikipedia
- Chemical Constituents from the Flowers of Wild Gardenia jasminoides J.Ellis – PubMed (2017)