Kuding Tea (Ilex latifolia, Ilex kudingcha, Ligustrum robustum): A Comprehensive Reference
1. Identity and Botanical Classification
1.1 Names and Taxonomy
Kuding tea (KT) is a bitter-tasting herbal tea that has been commonly used in traditional Chinese medicine (TCM). Also known as Kuding tea or Ku-Ding-Cha (Chinese: 苦丁茶; pinyin: kǔdīng chá), it is a bitter-tasting herbal infusion traditionally consumed in China and derived from the leaves of various evergreen plants, primarily from the genus Ilex in the Aquifoliaceae family.
The name "Kuding," meaning "bitter spike," reflects its distinct bitter taste, valued for its health benefits. Approximately 12 species belonging to different families and genera are collectively called "Ku-Ding-Cha" in different areas of China.
1.2 The Two Major Groups: Large-Leaved and Small-Leaved Kudingcha
KT is generally categorized into two types: "large leaved kuding tea" and "small leaved kuding tea." The main species of large-leaved KT are Ilex latifolia Thunb and Ilex kudingcha C.J. Tseng, while small-leaved KT typically refers to Ligustrum robustum. Other KT species have been successively identified, such as Ilex kaushue S.Y. Hu and Ilex pentagona S.K. Chen.
The other important group (the small-leaved Kudingcha) from the genus Ligustrum was first reported in the book of "Guizhou Min Jian Fang Yao Ji" in 1958. Some investigators put forward that the small-leaved Kudingcha originated from the mountains of Dalou and the river valley of Wujiang in Guizhou province. It has been used in the civilian Tujia ethnic group and Miao ethnic group for a long time, and was named as one of the four famous old tea species locally.
The large-leaved Kudingcha was certified to be the original Kudingcha species and has obvious antioxidant, anti-inflammatory, lipid metabolism, hepatoprotective, and anti-tumor activities, similar to the popular green tea (Camellia sinensis) and the Yerba maté tea (Ilex paraguariensis) from South America.
The small-leaved Kudingcha from the genus Ligustrum are shrubs or small trees, deciduous or evergreen. The leaves are much smaller and thinner than the large-leaved Kudingcha, and the flavor is not as bitter, which makes it more suitable to drink routinely.
1.3 Botanical Characteristics and Geographic Distribution
KT grows in a spiral formation, with leaf sizes ranging from 8 to 25 cm in length and 4.5 to 8.5 cm in width. It thrives in wet valleys, near streams, and in moist, dense forests. The trees can reach several meters in height, and the bark is typically black. KT is widely distributed across southern China, in provinces such as Hubei, Guangxi, Guangdong, and Hainan, where the ideal climate and soil conditions foster its cultivation.
Ilex latifolia Thunb. is found in regions like Hainan, Jiangxi, Jiangsu, and Zhejiang provinces, while Ilex kudingcha C.J. Tseng is native to Fujian, Guangxi, and Guangdong, along with small-leaved types from the genus Ligustrum in the Oleaceae family, collectively referred to as Ku-Ding-Cha.
1.4 Common Forms and Preparations
The traditional method involves withering fresh leaves under sunlight, followed by "killing green" to halt oxidation, rolling, and drying to preserve quality. One of the most visually distinctive commercial forms of the beverage involves rolling: the long, narrow leaves are twisted together to form distinctive long stick/spike-like shapes.
KT is no longer used only as a beverage. Various extraction methods have been applied to obtain partly purified extracts of KT. Over the last several years, Kudingcha has been considered as a dietetic beverage and is gaining popularity with names like "beauty-slimming tea," "longevity tea," "green-golden tea," and "clearing-heat tea."
As a beverage, kuding tea is prepared as a loose-leaf infusion, while standardized extracts of both the polyphenol and saponin fractions have been employed in research settings. KT has long been recognized as a Food & Medicine Homology product, known for its various active components and health benefits.
2. Traditional and Historical Use
2.1 History in China
In China, Kudingcha has been used for almost 2,000 years as a tea to quench thirst, remove phlegm, refresh the mind, and improve eyesight. These species have been utilized historically in ancient Chinese texts for their medicinal properties, such as in the Compendium of Materia Medica from the Ming Dynasty.
Historically, KT was used to treat heat-related ailments like fever and headaches during the Tang Dynasty (618–907 CE), primarily among the elite and practitioners of Traditional Chinese Medicine. Over time, KT gained broader popularity and was incorporated into Chinese culture as both a medicinal product and a daily beverage, reputed for promoting longevity and health.
During the Song dynasty, it was presented as a tribute tea to government officials. Later on, the production of Kuding tea increased and it became a popular folk medicine.
During the Ming and Qing dynasties, Kuding's use proliferated as a common household remedy, valued for its detoxifying properties and potential to promote longevity by clearing internal heat and toxins from the body.
By the 20th century, KT expanded to East Asian markets such as Japan and Korea, and its medicinal properties were promoted internationally as part of the global herbal products industry.
2.2 Traditional Chinese Medicine (TCM) Classification and Applications
The traditional Chinese medicinal properties associated with kuding include its ability to disperse fever, clear the head and the eyes, and resolve toxin, thus being used for common cold, rhinitis, itching eyes, red eyes, and headache.
In traditional Chinese medicine (TCM), Kuding has been used for centuries to dispel heat and toxins from the body, alleviate conditions like hypertension, hyperlipidemia, and obesity, and promote overall detoxification and digestive health.
In Traditional Chinese Medicine (TCM), Ku Ding Cha belongs to the "Herbs that anchor and calm the Spirit" category. These herbs are substances that tranquilize the Mind and treat symptoms such as restlessness, palpitations, anxiety or insomnia. They tend to have sedative properties by weighing the Qi downwards and should generally be used for a limited time only.
Furthermore, Ku Ding Cha is Cold in nature in TCM. This means that Ku Ding Cha typically helps people who have too much "Heat" in their body.
In traditional Chinese medicine, kuding tea has also been used in formulae for treating obesity, hypertension, cardiovascular disease, hyperlipidemia, and various other diseases.
Folk medicine traditions in China encapsulate kuding's reputation through the saying jiàng sān gāo (降三高), which translates to "reduce three highs," referring to the fact that this herb is associated with the ability to reduce high blood sugar (diabetes), high blood pressure, and high cholesterol.
2.3 Regional Ethnic Uses
Historically, Kuding leaves were primarily wild-harvested for centuries, as documented in traditional Chinese texts dating back nearly 2,000 years, though organized cultivation has occurred since at least the 18th century. Some investigators put forward that the small-leaved Kudingcha originated from the mountains of Dalou and the river valley of Wujiang in Guizhou province. It has been used in the civilian Tujia ethnic group and Miao ethnic group for a long time, and was named as one of the four famous old tea species locally.
3. Key Constituents and Phytochemistry
3.1 Overview of Bioactive Classes
KT is a promising and cost-effective product, containing numerous bioactive constituents, including polyphenols, triterpenoids, phenylethanoids, and polysaccharides, which exhibit strong antioxidant, anti-obesity, anti-diabetic, anti-inflammatory, neuroprotective, and anti-cancer activities.
Triterpenoids, phenolic acids, flavonoids, and essential oils were isolated and identified from the large-leaved Kudingcha. Among different types of constituents, triterpenoids and polyphenols were considered to be the most important metabolites, with various bioactivities.
KT and other non-camellia teas were reported to contain kinds of bioactive compounds, including polyphenols, flavonoids, terpenoids, polysaccharides, and saponins, with polyphenols and flavonoids being the dominant compounds.
3.2 Triterpenoids and Saponins (Kudinosides and Kudinlactones)
The main active components are triterpene glycosides (saponins), which have been dubbed kudinosides and kudinlactones. Triterpenes and their glycosides (saponins) are contained as bitter components, and a variety of them have been isolated from the plants that produce kuding, such as ursolic acid, lupeol, taraxerol, and uvaol. Additionally, β-sitosterol, a phytosterol, has been reported.
The ursane-type triterpenoids with lactone at the position of C20 and C28 are called α-kudinlactone, β-kudinlactone, and γ-kudinlactone, and are considered to be the most characteristic chemicals in the Kudingcha species. The chemical analysis showed that I. kudingcha had the highest total triterpenoid content.
KT is rich in polyphenols and saponins, including kudinosides, as well as chlorogenic acids (CGAs), which may be partly responsible for its bitterness. Other important constituents of KT comprise terpenoids, including the pentacyclic triterpenoid ursolic acid (UA).
3.3 Polyphenols: Caffeoylquinic Acids and Flavonoids
Caffeoyl quinic acid (CQA) derivatives have been identified as major phenolic compounds in Kuding tea. CQA derivatives have been isolated from the natural functional compounds of a variety of plants and have demonstrated pharmacological properties in numerous diseases, including as antioxidants, hepatoprotectants, antibacterial agents, antihistamines, and as anticancer and neuroprotective agents.
CGAs are a large family of esters formed between quinic acid and one to four residues of certain cinnamic acids, most commonly caffeic, p-coumaric, and ferulic. The distinctive characteristic of CGAs is that they usually have many isomers owing to the different substituted positions of cinnamic acids on quinic acid. In previous work, the isolation and structural identification of only 13 phenolic acids from Kuding tea have been reported.
KT and other non-camellia teas were reported to contain polyphenols, flavonoids, terpenoids, polysaccharides, and saponins, with polyphenols and flavonoids being dominant compounds. Flavonoids are usually categorized into flavonols, flavanols, flavones, isoflavones, flavanones, and anthocyanidins, possessing varied bioactivities.
Compared to green tea, catechins (about 1.7%) are reported to be less abundant, while rutin (about 0.4%) is more abundant. In addition, kuding is reported to contain more zinc, manganese, copper, and selenium, and less amino acids and ascorbic acid than green tea.
The polyphenol content in small-leaved Kuding tea (SLKDT) is as high as 6%, and thus SLKDT drink is viewed as a health product.
3.4 Polysaccharides
Kuding tea contains more than 200 ingredients, which include Kuding saponin, amino acid, vitamin C, polyphenols, flavonoids, and protein. Polysaccharides constitute another notable fraction that has been investigated separately for hepatoprotective and gastroprotective activities in preclinical models, and are distinguished from the phenolic and triterpenoid fractions in mechanistic research.
4. Mechanisms of Action
4.1 Lipid Metabolism: LXRβ Antagonism and ACAT Inhibition
Fan et al. found, by employing a transgenic reporter gene cell line, that the activation of liver X receptor-beta (LXRβ) by its agonist GW3965 was competitively inhibited by KTE. This may point to the underlying molecular mechanism, since LXRs are members of the nuclear receptor family of transcription factors and are important modulators of lipid and cholesterol homeostasis. In line with this, the expression levels of LXRβ target genes involved in fatty acid and cholesterol metabolism were significantly downregulated in KTE-treated mice.
Acyl CoA cholesteryl acyl transferase (ACAT) catalyzes the intracellular esterification of cholesterol in various tissues, and inhibitors of ACAT may serve as new types of medicines to treat arteriosclerosis and obesity. Compounds isolated from I. kudingcha showed potent inhibitory activity in the ACAT assay. It was likely that the saponins reduced the level of total cholesterol through the inhibition of ACAT activity.
4.2 Anti-inflammatory Pathways
In C57BL/7 mice with DSS-induced colitis, KTE treatment by intragastric gavage notably inhibited the production of proinflammatory cytokines and alleviated typical symptoms and the colitic histological changes of inflammatory bowel diseases. The highest orally administered dose of 1000 mg/kg led to the strongest reduction of approximately 50% of both IL-6 and tumour necrosis factor-alpha (TNF-α). KT polyphenols were identified as potent components exhibiting anti-inflammatory activity. The highest KT polyphenol dose (100 mg/kg BW) lowered serum proinflammatory cytokine levels of IL-6, TNF-α, and interferon-gamma (IFN-γ) to close to those of mice treated with the positive control ranitidine.
4.3 Neuroprotective Mechanisms
Kuding tea also significantly reduces middle cerebral artery occlusion and reperfusion (MCAO/reperfusion), induces infarction and neurological deficits and loss of neural cells, and inhibits the phosphorylation of mitogen-activated protein kinase and cyclooxygenase-2.
Unlike the proapoptotic effects on cancer cells, KTE prevented apoptotic neuronal death, thereby reducing ischaemic damage. Increased Bcl-2 levels and decreased Bax and caspase-3 levels were observed in KTE-treated rats. The inhibition of extracellular signalling-regulating kinases (ERK 1/2) and p38 MAPK phosphorylation by KTE was suggested to be the underlying mechanism that prevents apoptosis and, therefore, confers neuroprotection.
Extracts of I. latifolia (10–100 μg/mL) inhibited glutamate-induced neuronal death, elevation of intracellular calcium ([Ca²⁺]i), generation of reactive oxygen species (ROS), increase of a pro-apoptotic protein, BAX, and decrease of an anti-apoptotic protein, BcL-2. Hypoxia-induced neuronal cell death was also inhibited by I. latifolia. The neuroprotective effects on ischemia-induced brain damage might be associated with the anti-excitatory and anti-oxidative actions, and could be attributable to the active CQA compounds.
4.4 Antioxidant Mechanisms
Polyphenols from small-leaved Kuding tea (PSLKDT) upregulated neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), Cu/Zn-SOD, Mn-SOD, catalase (CAT), heme oxygenase-1 (HO-1), nuclear factor Nrf2, γ-glutamylcysteine synthetase (γ-GCS), and NQO1 mRNA expression, and downregulated inducible nitric oxide synthase (iNOS) mRNA expression. Protein levels of SOD1, SOD2, CAT, GSH1, and GSH2 in the liver and spleen were also increased by PSLKDT treatment.
4.5 Pro-apoptotic Effects on Cancer Cells
At 100 μg/mL, Kuding tea polyphenols significantly induced apoptosis in BcaCD885 cancer cells as determined by flow cytometry, where the content of sub-G1 cancer cells was 32.7%. Kuding tea polyphenol significantly induced apoptosis in BcaCD885 cancer cells by upregulating caspase-3, caspase-8, caspase-9, Fas/FasL, Bax, p53, p21, E2F1, p73 and downregulating Bcl-2, Bcl-xL, HIAP-1, and HIAP-2 mRNA and protein expressions.
4.6 Hepatic Enzyme Induction
KTE substantially increased the mRNA and protein levels of hepatic CYP3A and GSTA1, which are central to the detoxification of drugs and xenobiotics. A moderate elevation in hepatic CYP3A (5-fold change) and GSTA1 (1.7-fold change) mRNA levels was observed in ursolic acid-fed mice.
5. Scientific Evidence by Health Area
5.1 Lipid-Lowering Effects
Human/Clinical Evidence
The strongest body of human evidence for kuding tea concerns its effects on blood lipid profiles. KT has been found to have a lipid-lowering effect in clinical and experimental studies.
Eight electronic databases were searched from database inception until September 2021 for relevant randomized controlled trials (RCTs). Eight RCTs involving 716 patients were included in the meta-analysis. Comparing with the control group, the KT group reduced serum total cholesterol (TC) levels (WMD: −0.56 mmol/L; 95% CI: −0.64, −0.47; I² = 56.56%; P = 0.00), triglyceride (TG) levels (WMD: −0.30 mmol/L; 95% CI: −0.35, −0.24; I² = 88.60%; P = 0.00), and low-density lipoprotein cholesterol (LDL-C) levels (WMD: −0.29 mmol/L; 95% CI: −0.37, −0.21; I² = 89.43%; P = 0.00), but showed no significant effects on high-density lipoprotein cholesterol (HDL-C) (WMD: 0.07 mmol/L; 95% CI: −0.02, 0.16; I² = 93.92%; P = 0.12).
Subgroup analyses showed that KT intervention period was the source of heterogeneity. Following analysis, results revealed that long-term (>4 weeks and ≤8 weeks) use of KT increased HDL-C levels (WMD: 0.19; 95% CI: 0.13, 0.25).
Evidence assessment: Some clinical studies have reported that regular consumption of kuding tea may help lower blood pressure and support healthy cholesterol levels, though these studies often involve small sample sizes and short durations. The 2022 meta-analysis represents the highest level of aggregated clinical evidence to date, but the high heterogeneity (I² values up to ~93% for HDL-C) across the eight included RCTs limits confidence in the pooled estimates. The included trials were conducted predominantly in Chinese populations with metabolic disorders, which limits generalizability.
Preclinical (Animal/In Vitro) Evidence
In preventive treatment, kuding tea extract blocked body weight gain, reduced the size of adipocytes, and lowered serum triglyceride, cholesterol, LDL-cholesterol, fasting blood glucose levels, and glucose tolerance in high-fat diet-fed C57BL/6 mice. In therapeutic treatment, KTE reduced the size of the white adipocytes, serum TG, and fasting blood glucose levels in obese mice.
Kudingcha treatment led to greater inhibition of malondialdehyde (MDA) activity than atorvastatin in one experimental model.
5.2 Antidiabetic and Metabolic Effects
Several clinical studies have focused on its effects on lipid lowering, body weight reduction, and blood glucose lowering in patients with metabolic syndromes. The different extracts and active components from Kuding tea, including triterpenes, triterpenoid saponins, and chlorogenic acids (CGAs), have been reported to possess significant antidiabetic activity in vitro or in vivo.
KT exhibits antiobesity properties, possibly partly by affecting the intestinal microbiota. Several studies have focused on the antiobesity properties of KT. In particular, the effects of KT on lipid metabolism, body weight, and blood glucose have gained increasing attention. In this context, the intestinal microbiota has been identified as a putative novel target of KT.
Evidence assessment: Evidence for antidiabetic effects in humans is preliminary. Most data come from animal or in vitro studies. The clinical RCTs included in the 2022 meta-analysis involved patients with metabolic disorders including elevated blood glucose, but the primary outcome assessed was lipid profile rather than glycemic indices specifically. Dedicated, adequately powered clinical trials focused on glycemic outcomes have not yet been reported in peer-reviewed systematic reviews.
5.3 Anti-inflammatory Effects
Kuding made from L. robustum has similar anti-oxidative effects to tea in addition to additional anti-inflammatory properties.
Extracts and active components from Kuding tea have been reported to possess significant anti-inflammatory activity in vitro or in vivo.
Evidence assessment: Anti-inflammatory evidence is largely preclinical (rodent models and cell culture). Mechanisms involving NF-κB, MAPK, TNF-α, IL-6, and IFN-γ pathways have been identified in animal studies, but robust human trials specifically examining inflammatory markers as primary outcomes are not yet available.
5.4 Antioxidant and Anti-aging Effects
Results from in vivo research indicate that polyphenols from small-leaved kuding tea are effective in preventing D-galactose-induced oxidative aging in mice, and their efficacy is significantly higher than antioxidant vitamin C. Because PSLKDT is a potent antioxidant and antiaging polyphenol, Kuding tea rich in PSLKDT should be considered an ideal drink with antioxidative and antiaging effects.
Animal studies have shown that the phenolic constituents and phenylethanoid glycosides of kuding tea exhibit significant antioxidant activities in vitro.
Evidence assessment: Antioxidant and anti-aging effects are well-characterized at the in vitro and rodent model level. No controlled human trials specifically designed to assess antioxidant effects or anti-aging markers as primary outcomes have been identified in peer-reviewed systematic reviews.
5.5 Neuroprotective Effects
The results suggested that I. latifolia and its active compounds prevented glutamate-induced neuronal cell damage by inhibiting the increase of intracellular calcium, generation of ROS, and the apoptotic pathway. The neuroprotective effects on ischemia-induced brain damage might be associated with the anti-excitatory and anti-oxidative actions, attributable to CQA compounds.
Evidence assessment: Neuroprotective evidence is entirely preclinical (cell culture and animal models of stroke/ischemia). No human clinical trials specifically examining neuroprotective or cognitive outcomes with kuding tea have been identified in the peer-reviewed literature.
5.6 Anticancer Activities
After 25, 50, and 100 μg/mL of Kuding tea polyphenol treatment for 48 h, cell proliferation of human buccal squamous cell carcinoma cell line BcaCD885 was inhibited, and the 100 μg/mL of Kuding tea polyphenol showed the highest inhibitory rate at 72.3%. The 100 μg/mL of Kuding tea polyphenols significantly induced apoptosis as determined by flow cytometry analysis, with the content of sub-G1 cancer cells at 32.7%.
Although many constituents including phenolic acids and triterpenoids have been identified in KT, and their bioactivities such as antioxidant, anti-obesity, anti-inflammatory, anti-cancer, modulation of gut microbiota, and lowering lipid levels have been characterized, most studies focused on the isolation and characterization of bioactive compounds from certain original plants or products of KT.
Evidence assessment: Anticancer evidence is confined to in vitro cell-line studies and some animal work. No human clinical trials examining kuding tea as an anticancer intervention have been reported. In vitro findings in cancer cell lines cannot be directly extrapolated to clinical efficacy or safety in humans.
5.7 Hepatoprotective Effects
It has been shown that low dietary KT concentrations ameliorated hepatic lipid accumulation induced by a high-fat diet in mice.
Ursolic acid, a key constituent of KT, has been previously studied in the context of diet-induced non-alcoholic fatty liver disease (NAFLD) treatment.
Evidence assessment: Hepatoprotective evidence is limited to preclinical rodent models. Importantly, at high supplemental doses in concentrated extract form, adverse hepatic effects have been observed (see Safety section). Human data are absent.
5.8 Gut Microbiota Modulation
The effects of KT on lipid metabolism, body weight, and blood glucose have gained increasing attention. In this context, the intestinal microbiota has been identified as a putative novel target of KT.
Evidence assessment: Gut microbiota modulation evidence is entirely preclinical (primarily high-fat diet mouse models). The functional relevance of these shifts to human health outcomes remains to be established in clinical studies.
6. Body Systems and Health Areas Associated with Kuding Tea
- Cardiovascular system: Research may suggest that the herb, derived from either Ilex or Ligustrum, promotes blood circulation, lowers blood pressure, and lowers blood lipids, including cholesterol.
- Metabolic system: KT is used as a medicinal plant to manage hypertension, hyperlipidaemia, and obesity.
- Nervous system: KT has the reputation of preventing deterioration of the heart and brain function. The neuroprotective mechanisms identified include inhibition of glutamate-induced neuronal death and MAPK phosphorylation.
- Immune and inflammatory system: Active components from Kuding tea have been reported to possess significant anti-inflammatory activity in vitro or in vivo.
- Digestive system: KT polyphenols have shown gastroprotective and anti-colitic effects in animal models, including inhibition of proinflammatory cytokines in DSS-induced colitis.
- Hepatic system: These ingredients protect the vascular system, regulate lipid metabolism, and have antioxidant, hypoglycemic, and anti-tumor effects.
- Skin: Polyphenols derived from I. kudingcha were also reported to inhibit skin damage caused by ultraviolet B-induced skin injury in SKH1 hairless mice. The antioxidative and anti-inflammatory properties of KT polyphenols, plus the fact that they modulate skin proteins (MMPs, TIMPs), are probably responsible for their skin-protective properties.
7. Dosage Forms and Reported Dosages
Kuding tea is consumed or studied in several forms: traditional aqueous infusions of dried whole or rolled leaves, aqueous extracts, ethanol extracts, polyphenol-enriched fractions, saponin-enriched fractions, and polysaccharide fractions. More recently, extract-cyclodextrin (γ-CD) encapsulation complexes have been used in laboratory research.
The following dosages have been specifically reported in peer-reviewed studies:
- In male C57BL/6 mice fed a high-fat diet, supplementation with 400 mg/kg/d aqueous I. kudingcha extract was examined.
- In a two-week feeding study, injured rats were fed a control diet or the same diet supplemented with increasing doses of an aqueous extract of I. kudingcha. The highest orally administered dose of 1000 mg/kg led to the strongest reduction of approximately 50% of both IL-6 and TNF-α.
- The highest KT polyphenol dose (100 mg/kg BW) lowered serum proinflammatory cytokine levels of IL-6, TNF-α, and IFN-γ to close to those of mice treated with the positive control ranitidine.
- Male C57BL/6 mice were fed a high-fat, high-fructose, Western-type diet supplemented with either 12.88% γ-cyclodextrin (γCD), 7.12% KTE (comprising 0.15% ursolic acid, UA) encapsulated in 12.88% γCD (KTE-γCD), or 0.15% UA over a 6-week experimental period.
- In cell culture, after 25, 50, and 100 μg/mL of Kuding tea polyphenol treatment for 48 h, cell proliferation of human buccal squamous cell carcinoma cell line BcaCD885 was inhibited.
No standardized dosage for human consumption has been established through sufficiently powered clinical trials. Some clinical studies have reported effects with regular consumption, though these studies often involve small sample sizes and short durations. No official pharmacopeial monograph specifying human dosing for kuding tea has been identified in accessible sources at the time of this writing.
8. Safety Considerations
8.1 Acute Toxicity
In rats, doses up to 10,000 mg/kg given for 14 days by oral administration did not reach a death rate of 50%. Therefore, the median lethal dose (LD50) of kuding nanoparticles (KNP) was set at >10,000 mg/kg.
Serum and liver malondialdehyde (MDA) levels decreased after oral gavage of KNP for four weeks compared to high-fat diet control mice, while serum and liver SOD levels increased in KNP mice.
8.2 Hepatic Safety Concerns at High Extract Doses
In a recent study, high-dose dietary KTE supplementation in the form of KTE encapsulated in γCD (KTE-γCD) induced fatty liver and increased hepatic xenobiotic-metabolising enzymes in mice after a six-week intervention. Substantial induction of phase I and phase II enzymes and a phase III transporter of xenobiotic biotransformation was observed, indicating that the ingredients of KTE may interfere with xenobiotic/drug detoxification metabolism. In detail, induction of cytochrome P450, family 3, subfamily a (Cyp3a), glutathione S-transferase, alpha 1 (Gsta1) and ATP-binding cassette, subfamily C, member 3 (Abcc3) was reported.
Treatment with KTE-γCD, but not γCD and UA, increased liver weight and hepatic fat accumulation, which was accompanied by increased hepatic PPARγ and CD36 mRNA levels. KTE-γCD treatment also elevated plasma cholesterol and CYP7A1 mRNA and protein levels compared to those in control mice.
In vitro data collected in HepG2 cells indicated a dose-dependent increase in hepatic cytotoxicity in response to KTE treatment, which may have been partly mediated by ursolic acid.
8.3 Drug Interaction Potential
Herbal dietary supplements such as KTE and its constituents may interfere with drug metabolism, leading to altered drug bioavailability, increased toxicity, and/or the loss of therapeutic efficacy, which warrants further investigation.
In the relevant study, substantial induction of CYP3A and GSTA1 gene and protein expression was observed due to dietary KTE. Thus, herbal dietary supplements such as KTE and its constituents may interfere with drug metabolism. CYP3A is involved in the metabolism of a large fraction of pharmaceutical drugs, so induction of this enzyme system at high extract doses raises the potential for clinically meaningful pharmacokinetic interactions. This finding was made in a mouse model using a concentrated, encapsulated extract, and its direct applicability to typical beverage consumption in humans is not established.
8.4 Species Authenticity and Adulteration Risk
No literal records for small-leaved Kudingcha have been found in ancient books to date. The small-leaved Kudingcha (L. robustum) was initially used because of its similarities in plant morphology, bitter flavor, and ethnobotanical use. Because the term "kuding tea" applies collectively to species from two distinct plant families (Aquifoliaceae and Oleaceae), the chemical composition, pharmacological profile, and safety data for one source plant may not be directly applicable to another, and source authentication is an important consideration in research and commercial contexts.
8.5 Safety Data Gaps
Kuding tea (KT) is a traditional Chinese beverage rich in plant bioactives that may exhibit various health benefits. However, little is known about the safety of KT extract (KTE) when consumed long term at high doses as a dietary supplement. Formal safety evaluations in humans, particularly for concentrated extracts used as supplements rather than traditional tea infusions, remain limited.
References
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- "Chemical components, health-promoting effects and industrial application of a Chinese bitter tea (Kuding tea): A comprehensive review." Food Chemistry, 2025.
- Kuding – Wikipedia
- Jiang Z. et al. "Lipid-Lowering Efficacy of Kuding Tea in Patients With Metabolic Disorders." Frontiers in Nutrition, 2022. Full text.
- "Comparison analysis of bioactive constituents and heavy metals among original plants of Kuding tea from the genus Ilex." Arabian Journal of Chemistry, 2024.