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Oldenlandia diffusa

Table of contents

Other Names

Bai hua she she caoBáihuā shéshécǎoBaihuasheshecaoBonjalukDaniriDing jing caoFuta-ba muguraHedyotis brachypodaHedyotis diffusaHedyotis diffusa var. extensaHedyotis diffusa var. longipesHedyotis diffusa Willd.Hedyotis extensaHedyotis herbaceaHedyotis polygonoidesHedyotis radicansHedyotis ramosissimaHerba Hedyotidis DiffusaeHerba OldenlandiaeOldenlandia angustifolia var. pedicellataOldenlandia brachypodaOldenlandia brachypoda DC.Oldenlandia brachypoda Zoll. ex Miq.Oldenlandia corymbosa var. unifloraOldenlandia diffusa var. extensaOldenlandia diffusa var. polygonoidesOldenlandia herbacea var. unifloraOldenlandia paucifloraScleromitrion diffusumShéshécǎoSnake needle grassSnake tongue grassSpreading diamond flowerSpreading hedyotisUlasiman-kalatWhite flower snake-tongue grassフタバムグラ白花蛇舌草蛇舌草

Synopsis

Oldenlandia diffusa (Bai Hua She She Cao): A Comprehensive Reference

1. Identity and Botanical Classification

Nomenclature and Taxonomy

Oldenlandia diffusa (Willd.) Roxb. is a species of flowering plant in the family Rubiaceae. The taxonomy of this plant is notably complex. Synonyms of the accepted name include Hedyotis diffusa Willd. and Scleromitrion diffusum (Willd.) R.J.Wang — homotypic synonyms recognised by Plants of the World Online as of March 2023, which treats the taxon as Scleromitrion diffusum.

The taxonomy of this and related species is complicated, and different authors have drawn very different conclusions. In most of the pharmacological and phytochemical literature the plant is referred to as either Oldenlandia diffusa or Hedyotis diffusa Willd., and these names should be understood as referring to the same medicinal entity for research purposes.

The plant's pharmaceutical name is Herba Hedyotis Diffusae (also written Herba Oldenlandiae). It is also known by the alternate Latin botanical name Hedyotis diffusa, the pharmaceutical name Herba hedyotis diffusae, and the Pin Yin name Bai hua she she cao. In traditional Chinese medicine the plant is known as 白花蛇舌草 (báihuā shéshécǎo), meaning "white flower snake-tongue grass."

Morphology and Natural Habitat

Oldenlandia diffusa is a slender, annual plant with ascending to procumbent, more or less branched stems up to 50 cm long. It is found mainly in the south-eastern provinces of China and grows at low altitudes in moist fields. Roxb. is a plant commonly used in Chinese traditional medicine and is widely distributed in the southern provinces of China.

Common Forms and Preparations

The herb is used in multiple preparation forms. A decoction is traditionally used as a treatment. Commercially and in research, preparations include dried powdered whole herb (Herba Oldenlandiae), water extracts (decoctions), ethanol/methanol extracts, and isolated fractions containing concentrated flavonoids, iridoids, or individual compounds such as ursolic acid. It is sometimes combined with Siraitia grosvenorii and Scutellaria barbata to make hot drinks.

Quality Control and Adulteration

Quality control issues have been reported. Two similar species — O. corymbosa LAM and Oldenlandia tenelliflora BL — are commonly used as substitutes for Herba Oldenlandiae (the powdered form of O. diffusa). Another herb, O. corymbosa (L.) Lam, is also used interchangeably in South China for treating the same conditions. This substitution introduces research and clinical inconsistencies, as the two species differ in their chemical profiles.


2. Traditional and Historical Use

Traditional Chinese Medicine (TCM)

Oldenlandia diffusa, prevalent in East Asia and Southern China, is used in traditional Chinese medicine to clear "heat" and to eliminate "toxins." It is used in combination with other herbs for the treatment of hepatitis, snake bites, and tumors of the liver, lung, stomach, and rectum.

O. diffusa is commonly used in Southern China for the treatment of hepatitis, tonsillitis, sore throat, appendicitis, urethral infection, and malignant tumors of the liver, lung, and stomach. It has been used for the treatment of inflammation-linked diseases, such as hepatitis, appendicitis, and urethritis in traditional Chinese medicine.

In TCM theory, the herb is classified by its taste and thermal properties. An Illustrated Guide to Antineoplastic Chinese Herbal Medicine lists the properties and indications of oldenlandia as: sweet, bland, slightly bitter, and slightly cold. It clears heat and toxin, activates blood circulation, removes blood stasis, promotes diuresis, and relieves stranguria (urinary obstruction). Indications include various kinds of tumors, especially tumors of the digestive tract, lymphosarcoma, and carcinoma of the liver and larynx.

In TCM, Oldenlandia diffusa is believed to "clear heat" and "eliminate toxins," and is often employed for conditions involving the urinary tract, such as urinary tract infections, stranguria (painful urination), and damp-heat conditions affecting the bladder. Historical texts and modern TCM formularies frequently list this herb as a supportive agent for urinary health, especially when there are symptoms of infection or inflammation.

Historical Prominence and Folk Medicine

The herbs had been utilized in some folk remedies in the past, but came to prominence only during the 20th Century. Oldenlandia has one of the longest of Chinese herb names, outdoing even cordyceps when it comes to today's commonly used herbs. It is a popular folk medicine and is typically prescribed for the treatment of lung, liver, and rectal cancers.

In 1975, it was claimed that beneficial effects could be achieved in those cases of cancer resistant to other therapies and that the herb could be used synergistically with or alternating with other anticancer drugs.

Use in Korea and Other East Asian Traditions

OD is a well-known medicinal plant used in Korean and Chinese herbal medicine for the treatment of hepatitis, tonsillitis, urethral infection, and malignant tumors of the liver and lung. Oldenlandia diffusa has been used as a natural drug for the treatment of cancer in Asia and specifically in Korea.

Traditional Preparations

Preparations used historically include water decoctions of the whole plant, poultices applied topically, and infusions. Hedyotis diffusa Willd. has been used as a major component in several Chinese medicine formulas for the clinical treatment of colorectal cancer. It is frequently prescribed in combination with Scutellaria barbata (Ban Zhi Lian) for oncological indications. Traditional Chinese medicine is the most common type of complementary and alternative medicine used in Taiwan and is increasingly used to treat patients with cancer. O. diffusa is already used for clinical colon and breast cancer treatments in Taiwan.


3. Key Chemical Constituents and Active Compounds

Overview of Phytochemical Classes

The Oldenlandia genus comprises approximately 240 species of plants, yet only a limited number have been investigated for their chemical composition and medicinal properties. These species contain a wide range of compounds such as iridoids, anthraquinones, triterpenes, phytosterols, flavonoids, anthocyanidins, vitamins, essential oils, phenolic acids, and coumarins. These diverse phytochemical profiles underscore the pharmacological potential of Oldenlandia plants for various medical purposes.

At present, more than 180 compounds have been found from Hedyotis diffusa Willd., including iridoid terpenes, flavonoids, anthraquinones, phenols, and other substances. Around 171 pharmacologically active compounds of O. diffusa have been reported.

Iridoid Glucosides

Major components of O. diffusa include iridoid glucosides, triterpenoids, flavonoids, and polysaccharides. Iridoid glucosides (IGs), the main terpene-derived components of O. diffusa, possess anti-tumor, anti-inflammatory, anti-oxidant, and anti-angiogenic activities. Specific iridoids identified include asperuloside, deacetyl asperuloside, geniposide, 10-dehydrogeniposide, daphylloside, diffusoside A, diffusoside B, scandoside methyl ester, acetyl scandoside methyl ester, deacetylasperulosidic acid methyl ester, gardenoside, and galioside, among others, isolated from the water extract.

Triterpenoids: Ursolic Acid and Oleanolic Acid

Among other chemical constituents, ursolic acid stands out as the most important active compound in Oldenlandia, owing to its proven anticancer, anti-inflammatory, antimicrobial, and hepatoprotective properties. Ursolic acid and oleanolic acid have been reported to have anti-tumor, apoptotic, antioxidant, cytotoxic, and anti-angiogenic activity, and anti-inflammatory effects.

Notably, ursolic acid and oleanolic acid differ in their biological activities despite being structural isomers. Among the samples tested, oleanolic acid (OA), but not the structural isomer ursolic acid (UA), inhibits the growth of ras oncogene-transformed R6 cells at a dosage that is not toxic to the co-cultivated normal fibroblasts. On the other hand, ursolic acid, a main component of methanol extracts not found in aqueous extracts of O. diffusa, exhibited significant antitumor effects.

Flavonoids

The total flavonoids of Hedyotis diffusa (FOD) are the main active components of Hedyotis diffusa Willd., most of which are the derivatives of flavonol aglycone of kaempferol and quercetin. Nine compounds have been isolated and identified, including quercetin and quercetin glycosides (quercetin-3-O-[2-O-(6-O-E-sinapoyl)-β-D-glucopyranosyl]-β-glucopyranoside, quercetin-3-O-[2-O-(6-O-E-feruloyl)-β-D-glucopyranosyl]-β-glucopyranoside), kaempferol glycosides, rutin, and quercetin.

Anthraquinones

Phytochemical studies revealed 8 anthraquinone compounds in the herb of H. diffusa. The first three anthraquinones isolated were identified as 2-methyl-3-hydroxyanthraquinone, 2-methyl-3-methoxy-anthraquinone, and 2-methyl-3-hydroxy-4-methoxyanthraquinone. Additional anthraquinones identified in more recent studies include 2,6-dihydroxy-1-methoxy-3-methylanthraquinone, 2-hydroxy-1-methoxy-3-methylanthraquinone, and 2-hydroxy-3-methylanthraquinone.

Other Compounds

Previous studies have indicated that OD contains many chemicals, including triterpenoids, ferulic acid, sterols, iridoid glycosides, polypeptides, flavonoids, ursolic acids, oleanolic acids, and polysaccharides, some of which have multiple effects such as anti-inflammatory, antioxidative, and immunoregulatory. Two new alternariol derivatives, 9-O-(trans-p-coumaroyl)-alternariol and 9-O-(trans-caffeoyl)-alternariol, have been isolated. Additional compounds include coniferin, loliolide, and (+)-neo-olivil. Identified active anticancer constituents include scopoletol, quercetin, ferulic acid, coumarin, and trans-4-methoxycinnamyl alcohol.

The plant has various active phytochemicals such as flavonoids, anthraquinones, terpenoids, sterols, and polysaccharides. Immunomodulatory glycoproteins have also been identified: the active immunomodulating components of Oldenlandia diffusa had an apparent molecular weight of 9–200 kD and were sensitive to pronase E and NaIO4 treatment, suggesting glycoproteins in nature.


4. Established Mechanisms of Action

Anticancer Mechanisms

Studies conducted in vitro and in animals have shown that O. diffusa exerts antitumor effects via apoptosis, dose-dependent increase of oxidative burst, caspase-dependent apoptosis, and apoptosis in a cell-cycle-independent fashion, possibly via induction of genotoxic damage.

STAT3 Pathway Suppression: EEHDW inhibited the phosphorylation of STAT3 in CRC mice, whereas the level of non-phosphorylated STAT3 remained unchanged after EEHDW treatment, suggesting that EEHDW significantly suppresses the activation of STAT3 in vivo. EEHDW treatment suppressed STAT3 phosphorylation in tumor tissues, which in turn resulted in the promotion of cancer cell apoptosis and inhibition of proliferation. EEHDW treatment altered the expression pattern of several important target genes of the STAT3 signaling pathway, including decreased expression of Cyclin D1, CDK4, and Bcl-2, as well as up-regulated p21 and Bax.

AMPK/mTOR Signaling: ODE exerted potent anti-proliferative, cytotoxic, and pro-apoptotic activities against established CRC lines and primary patient-derived human CRC cells. ODE activated AMP-activated protein kinase (AMPK) signaling, which led to subsequent mTORC1 inhibition and Bcl-2/HIF-1α downregulation in CRC cells. In ODE-treated CRC cells, AMPKα1 formed a complex with p53, which may be important for p53 activation and subsequent cancer cell apoptosis.

Endoplasmic Reticulum Stress in HCC: Using both in vitro and in vivo models, FOD was confirmed to inhibit HCC proliferation and induce apoptosis and autophagy. Mechanistic studies have shown that FOD induces apoptosis and activates autophagy in HCC cells by inducing endoplasmic reticulum stress (ER stress) and activating the PERK-eIF2α-ATF4 signaling pathway.

IL-6/STAT3 Axis in CRC: The interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway mediates the proliferative and anti-apoptotic activities required for oncogenesis under inflammatory conditions; thus, suppressing tumor growth by targeting the IL-6/STAT3 pathway is a promising therapeutic strategy for CRC.

Breast Cancer: O. diffusa extracts exert antiproliferative and apoptotic effects on human breast cancer cells through ERα/Sp1-mediated p53 activation.

Anti-Inflammatory Mechanisms

OD inhibited the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and prostaglandin E2 (PGE2). OD inhibited the enhanced levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) induced by LPS. The anti-inflammatory effect of OD occurs via the regulation of the activation of nuclear factor (NF)-κB and caspase-1.

Immunomodulatory Mechanisms

In mouse peritoneal macrophages, OD regulates nitric oxide (NO) production. When OD (1 mg/ml) was used in combination with 10 U/ml of recombinant interferon-gamma (rIFN-gamma), there was a marked cooperative induction of NO production (36.13 ± 7.12 μM). Treatment of macrophages with rIFN-gamma plus OD (1 mg/ml) caused a significant increase in TNF-α production (4.49 ± 1.43 ng/ml). The increased production of NO and TNF-α from rIFN-gamma-plus OD-stimulated cells was almost completely inhibited by pretreatment with 100 μM of pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. PDTC also inhibited phosphorylation of IκB in rIFN-gamma-plus OD-stimulated cells.

Immunomodulating effects may occur through immune system stimulation to kill or engulf tumor cells. It has been suggested that the aqueous extract of O. diffusa has immunomodulating activity and it may stimulate the immune system to eliminate tumor cells.


5. Scientific Evidence by Area of Use

5.1 Oncology / Anticancer Effects

Overall evidence assessment: The large majority of anticancer evidence is preclinical (in vitro and animal models). Oldenlandia diffusa has shown anticancer effects in lab studies, but human data are lacking.

In Vitro Evidence

The water extract of the raw herb was tested for in vitro anti-proliferative activities against eight cancer cell lines and one normal cell line; microscopic examination and DNA ladder analysis were carried out to determine the pro-apoptotic effect of the extract. The extract exhibited strong antiproliferative activity against all cancer cell lines tested. The concentrations of growth inhibition at 50% (IC50) ranged from 7 to 25 mg raw material/ml after 48-hour treatment.

The water extract of Oldenlandia diffusa has been shown to be equally cytotoxic to both drug-sensitive (H69) and multidrug-resistant (H69VP) small cell lung carcinoma cell lines, inducing apoptosis in both cell types while being significantly less cytotoxic to normal lung epithelial cells. In a separate study, water extracts of Oldenlandia diffusa were found to be toxic to three pancreatic cancer cell lines in vitro, while being significantly less cytotoxic to normal pancreatic cells.

Results showed that Oldenlandia diffusa significantly inhibited the growth of HL60s and induced apoptosis in a cell cycle-independent fashion, possibly through the induction of genotoxic damage. Oldenlandia diffusa did not induce apoptosis in the PBLs (peripheral blood lymphocytes); however, progression through the cell cycle was not evident in stimulated PBLs, suggesting some degree of cytotoxicity.

ODE (25–200 μg/mL) induced significant apoptosis activation in HCT-116 cells. Caspase-3 activity, Histone DNA ELISA results, and the percentage of Annexin V or TUNEL positive cells were all increased following ODE treatment. The expressions of cleaved-PARP and cleaved-caspase-3 were increased in ODE-treated HCT-116 cells.

All isolates were evaluated for in vitro cytotoxic activities on MCF-7, HepG2, A549, and A2780 cancer cells. The new compounds 9-O-(trans-p-coumaroyl)-alternariol and 9-O-(trans-caffeoyl)-alternariol exhibited potent cytotoxic activities on A2780 (ovarian) cancer cells with IC50 values of 3.1 and 9.4 μM, respectively.

Animal Model Evidence

In vivo studies were carried out to examine the anticancer activities of the extract using C57BL/6j mice bearing B16-F10 lung metastasis. Oldenlandia diffusa extract was given at the dose level of 5 g raw material/kg on Days 3–12 by oral gavage and the extent of lung metastases were examined on Day 14.

Oral administration of O. diffusa to mice significantly inhibited the growth of murine renal carcinoma cells and O. diffusa extracts enhanced macrophage function in vitro. Polysaccharides isolated from O. diffusa also showed antitumor activities against transplanted Sarcoma-180 cells in mice.

The principal components oleanolic acid and ursolic acid showed anticancer effects including cytotoxicity, antiproliferation activity, and reduced migration ability in hepatocellular carcinoma cells. OD's therapeutic effect was investigated both in vitro and in a chemically induced HCC model; OD significantly enhanced apoptosis and antiproliferative activity and reduced migration ability of HCC cells.

Using a CRC mouse xenograft model, EEHDW could inhibit cancer growth in vivo, without any noticeable toxicity.

Colorectal Cancer: STAT3 and AMPK Pathways

O. diffusa ethanol extracts suppress the proliferation of colorectal cancer cells and induce cell apoptosis mediated by the suppression of the STAT3 pathway in mouse xenograft models and in human HT-29 cells. EEHDW inhibits the growth of the CRC HT-29 cell line via the IL-6/STAT3 signaling pathway. Pretreatment of HT-29 cells with IL-6 led to an increase in cell viability, colony formation, and phosphorylated STAT3 (p-STAT3) expression.

Human/Clinical Evidence

The traditional basis for its use is steeped in the principles of TCM; however, the scientific basis for its effectiveness is yet to be fully elucidated. Lab and animal studies suggest anticancer properties, but human data are lacking. As of the available literature, no large-scale randomized controlled clinical trials in humans specifically evaluating O. diffusa monotherapy for cancer treatment have been published. Its use in Taiwan appears to be observational and in combination formulas. The inconsistent laboratory results have been a barrier to more extensive use of oldenlandia for cancer in modern medicine. Nonetheless, oldenlandia was being utilized clinically by traditional medicine doctors.

5.2 Anti-Inflammatory Effects

Animal studies attribute anti-inflammatory activity to inhibition of TNF-α, IL-6, and prostaglandin E2 (PGE2). Animal studies show that certain chemicals found in this herb may help lower cholesterol and have anti-inflammatory effects.

In the context of rheumatoid arthritis, in China, Oldenlandia diffusa has been prescribed as a therapeutic herb for rheumatoid arthritis (RA). Preliminary studies of its anti-inflammatory effect in collagen-induced arthritis (CIA) rat models have been conducted. Ferulic acid, one constituent of OD, has been reported to have a beneficial effect on adjuvant arthritis treatment by reducing the level of IL-15 and IL-23, and to have a curative effect on RA by influencing the expression of serum VEGF and TNF-α. This evidence is preclinical (animal model); no human clinical trials in RA specifically for O. diffusa monotherapy have been identified in the searched literature.

5.3 Hepatoprotective Effects

The herb is well-known in Chinese folk medicine for the treatment of hepatitis and malignant tumors of the liver, lung, and stomach. Hepatitis: there are no data to support this claim in terms of controlled human trials, according to Memorial Sloan Kettering Cancer Center's integrative medicine database. The flavonoids as the main bioactive substances exhibit a wide spectrum of pharmacological activities, including hepatoprotective effects. Evidence at present is limited to in vitro and animal studies.

5.4 Immunomodulatory Effects

Several in vitro and animal studies point to immunomodulatory activity. Chinese medicinal herbs including O. diffusa enhanced the production of immunoglobulin, enhanced the induction of allo-antigen-specific cytotoxic T lymphocytes, had no effect on natural killer cells, and stimulated macrophages to produce interleukin-6 and tumor necrosis factor. Oral administration of O. diffusa to mice significantly inhibited the growth of murine renal carcinoma cells, and O. diffusa extracts enhanced macrophage function in vitro. Clinical immunomodulatory evidence in humans is absent from the published peer-reviewed literature.

5.5 Antioxidant Effects

The total flavonoids of Oldenlandia diffusa (FOD) are the main active components in Oldenlandia diffusa, which have anti-inflammatory, antioxidant, and anti-tumor effects. Antioxidant studies are largely in vitro, and the clinical relevance of these findings in humans has not been established.

5.6 Antibacterial and Anti-Infective Effects

Oldenlandia diffusa is an important Chinese traditional medicine with various biological activities such as anti-tumor, anti-inflammatory, anti-oxidant, antibacterial, neuroprotective, and hepatoprotective effects. Some laboratory studies have demonstrated modest antibacterial activity against pathogens that may cause urinary tract infections, but these findings have not yet translated into well-controlled human trials or standard medical recommendations.

5.7 Neuroprotective Effects

Oldenlandia diffusa has various biological activities including neuroprotective effects. Neuroprotective activity has been described in the literature, though as with other areas, the available evidence is preclinical and primarily based on cell culture and animal model data. No human clinical trials in this domain have been identified.


6. Body Systems and Health Areas of Association

  • Oncology / Immune-Oncology: Multiple biological activities of OD have been reported, including antitumor, chemopreventive, anti-inflammatory, antioxidant, and proapoptotic effects. Principal tumor types studied include liver, colorectal, breast, lung, pancreatic, and ovarian cancers, as well as leukemia.
  • Liver / Hepatic System: Well-known in Chinese folk medicine for the treatment of hepatitis and malignant tumors of the liver.
  • Immune System: Laboratory studies suggest that this herb may inhibit the growth of cancer cells and stimulate the immune system to destroy or engulf tumor cells.
  • Digestive/Gastrointestinal System: Historical TCM texts and modern herbal compendia describe its use for "intestinal abscesses," inflammatory bowel conditions, and as an adjunct in colorectal cancer management.
  • Urinary System: In TCM, Oldenlandia diffusa is believed to "clear heat" and "eliminate toxins," and is often employed for conditions involving the urinary tract, such as urinary tract infections and stranguria.
  • Musculoskeletal / Rheumatological System: Oldenlandia diffusa plays a key role in the herbal prescriptions for RA and has been shown to have immunomodulatory activity.
  • Nervous System: Neuroprotective properties have been identified in preclinical research, as reported among the documented biological activities of O. diffusa.

7. Dosage Forms and Dosages Reported in Studies

The following dosages are drawn exclusively from peer-reviewed studies and should not be interpreted as dosing recommendations:

  • In the B16-F10 lung metastasis mouse model, Oldenlandia diffusa extract was given at the dose level of 5 g raw material/kg on Days 3–12 by oral gavage.
  • In macrophage studies, OD at 1 mg/ml in combination with 10 U/ml of recombinant interferon-gamma (rIFN-gamma) produced marked cooperative induction of NO production.
  • In the HCC cell line study, cytotoxicity was measured with indicated concentrations of OD (0–500 mg/mL) for 24 hours, and antiproliferative activity was measured at OD 200 mg/mL against HCC cells for 72 hours.
  • ODE at concentrations of 25–200 μg/mL induced significant apoptosis activation in HCT-116 (colorectal cancer) cells.
  • The in vitro IC50 values for growth inhibition ranged from 7 to 25 mg raw material/ml after 48-hour treatment across eight cancer cell lines.
  • The newly isolated alternariol derivatives exhibited cytotoxic activities on A2780 cancer cells with IC50 values of 3.1 and 9.4 μM, respectively.

No standardized human clinical dosage has been established in the peer-reviewed literature. Traditional TCM decoctions are typically prepared from dried whole herb, but specific gram amounts per dose vary across formularies and combinations.


8. Safety Considerations and Drug Interactions

General Safety Profile

More research is necessary to confirm whether this herb can be used safely and effectively for any condition in humans. Systematic human safety studies are lacking. Its use is primarily justified by tradition rather than robust scientific evidence.

Cytochrome P450 Interactions

A rat pharmacokinetic study using a cocktail method evaluated the effect of O. diffusa on major CYP450 enzymes. Influences of Oldenlandia diffusa on the activities of five CYP450 subtypes were evaluated by five specific probe drugs (phenacetin for CYP1A2, omeprazole for CYP2C19, tolbutamide for CYP2C9, metoprolol for CYP2D6, and midazolam for CYP3A4). No statistically significant difference (P > 0.05) in pharmacokinetic behaviors was observed for any of the five probe drugs. This research showed that Oldenlandia diffusa had no effect on CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. There is potential guidance that Oldenlandia diffusa might be considered a safety combination drug with five CYPs metabolism drugs in clinical use. These findings are from animal (rat) studies and require confirmation in human pharmacokinetic trials.

Cancer Cell vs. Normal Cell Selectivity

Some preclinical data suggest preferential cytotoxicity toward cancer cells over normal cells. The water extract of Oldenlandia diffusa has been shown to be equally cytotoxic to both drug-sensitive and multidrug-resistant small cell lung carcinoma cell lines, inducing apoptosis in both cell types while being significantly less cytotoxic to normal lung epithelial cells. In a separate study, water extracts were found to be toxic to three pancreatic cancer cell lines in vitro, while being significantly less cytotoxic to normal pancreatic cells. However, these selectivity findings are in vitro and their translatability to humans is unknown.

Species Substitution Risk

Quality control issues have been reported. Two similar species — O. corymbosa LAM and Oldenlandia tenelliflora BL — are commonly used as substitutes for Herba Oldenlandiae. Because the chemical compositions of these species differ, substitution may result in altered efficacy or safety profiles, and correct botanical identification is critical.

Pregnancy and Specific Populations

No controlled clinical trials addressing the safety of O. diffusa in pregnancy, lactation, pediatric, or geriatric populations have been identified in the peer-reviewed literature reviewed for this article. TCM practice literature notes caution in use during pregnancy, though this is based on traditional contraindication principles rather than clinical trial data.

Evidence Strength: Overall Summary

Scientific studies on Oldenlandia diffusa have focused mostly on its anti-inflammatory, antibacterial, and anticancer properties, but these investigations are generally preliminary, often conducted in vitro or in animal models. Both O. diffusa and O. corymbosa have documented medicinal properties, but the identity, biosynthesis, and mode of action of the bioactive metabolites are still largely unknown. The body of evidence, while broad in preclinical scope, has not yet been translated into high-quality human clinical trials for any indication.

References

Health Conditions

Health conditions that Oldenlandia diffusa may help support.

  • No conditions available.

Body Systems

Body systems that Oldenlandia diffusa may help support.

  • No body systems available.
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