Synergistic Herbal Trios: Detoxification and Cellular Defense

TL;DR#

• AMPK activation [AN/PR]: well established for berberine (Coptis) across liver, muscle and fat models with clinical metabolic data; shown for Houttuynia in one hepatic cell model; no direct AMPK evidence for any Smilax species (CONFIDENCE: HIGH for berberine mechanism, MODERATE for clinical outcomes)
• Nrf2 pathway [AN]: mechanistically proven for berberine, where the AMPK-Nrf2 crosstalk carries the anti-inflammatory effect, and for S. glabra flavonoids in a lead-toxicity model; Houttuynia's antioxidant activity is documented but Nrf2 agonism itself is unproven (CONFIDENCE: HIGH for berberine, MODERATE for S. glabra, LOW-MODERATE for Houttuynia)
• Endotoxin antagonism [AN]: berberine is the direct LPS antagonist, entering the TLR4/MD-2 pocket; in mice it increased survival under Salmonella challenge without any bacteriostatic effect, protection the authors attribute to endotoxin-signalling blockade. Smilax flavonoids act differently, suppressing TLR4 and MyD88 protein overexpression rather than binding LPS (CONFIDENCE: MODERATE)
• NF-κB suppression [AN/PR]: all three herbs, at distinct levels: berberine suppresses LPS-induced NF-κB output through the AMPK-Nrf2 axis, with receptor-level LPS antagonism upstream at TLR4/MD-2 [6,8], Houttuynia blocks IκBα phosphorylation plus p38/JNK [2], Smilax flavonoids down-regulate the TLR4/MyD88 complex upstream [9] (CONFIDENCE: HIGH for mechanism, LOW for clinical outcomes)
• Pharmacokinetics [AN]: berberine alters the pharmacokinetics of CYP3A and P-glycoprotein substrates (Qiu 2009) - a drug-interaction hazard for narrow-therapeutic-index drugs, not a formulation strategy. The 2023 claim that sarsaparilla saponins enhance absorption has been removed as unsupported (CONFIDENCE: HIGH for the interaction)
• Antimicrobial [AN]: ten batches of Rhizoma coptidis showed anti-MRSA activity, including against a norA efflux-positive strain, with spectrum-effect analysis attributing activity to five protoberberine alkaloids (Luo 2014) (CONFIDENCE: MODERATE, in vitro)
• Caution: high-dose berberine warrants clinical supervision with digoxin, ciclosporin or tacrolimus-type drugs; avoid in pregnancy and lactation

Coptis chinensis (Chinese goldthread), Houttuynia cordata (fish mint), and Smilax regelii (sarsaparilla) are combined in traditional protocols and are examined here through a network-pharmacology lens. Unlike single-target pharmaceuticals, each herb engages multiple nodes across inflammatory, antioxidant and metabolic signalling. Whether the combination is genuinely synergistic is an open question: no isobologram, combination-index or network-pharmacology study of this specific trio exists, so "synergy" here means mechanistic complementarity, which is a hypothesis rather than a demonstrated effect.

Scope and Species Caveat#

Two caveats govern everything below.

First, Smilax regelii itself has almost no dedicated mechanistic pharmacology in the indexed literature. The Smilax evidence base is S. china, S. glabra and S. ornata, congeneric species sold interchangeably as sarsaparilla, and commercial sarsaparilla is a species mix to begin with. Extrapolation from congeners is pharmacologically reasonable, but it is extrapolation, and every Smilax claim below carries that label.

Second, Coptis chinensis is studied almost entirely as its rhizome (Rhizoma coptidis, in documented use for over two thousand years [1]) and its alkaloid berberine, while Houttuynia cordata is studied as whole-plant extracts, ethyl-acetate fractions and fermented preparations [2,3,4].

The 2026 revision corrected three mechanism assignments from the 2023 text: direct LPS antagonism belongs to berberine (Coptis), not to sarsaparilla saponins; P-glycoprotein interaction likewise belongs to berberine; and "all three herbs activate Nrf2" was reduced to the two herbs where Nrf2 activation is documented. Four of the five references in the 2023 version were also found to point to the wrong papers and have been replaced with verified sources.

Master Regulatory Pathways and Cellular Defense Mechanisms#

Evidence Level: [AN/PR] - Cell and animal studies for AMPK/Nrf2 mechanisms, limited human trials CONFIDENCE: HIGH for mechanistic pathways, LOW-MODERATE for clinical outcomes

AMPK Activation: The Metabolic Master Switch#

AMP-activated protein kinase activation is the best-characterised axis in this trio, and it is carried by one herb.

Coptis chinensis (berberine):

• AMPK activation with metabolic benefit in diabetic and insulin-resistant models: improved glucose tolerance, insulin sensitivity, and lipid handling [5]
• Downstream lipogenic suppression (FAS, SREBP-1c) and enhanced glucose uptake
• The 2023 list of berberine intracellular effects (complex I inhibition, GLUT4 translocation, ACC inhibition, mTOR inhibition) is consistent with this literature but is carried here at the level of the verified AMPK-activation finding

Houttuynia cordata (one model):

• An ethyl-acetate fraction attenuated lipid accumulation in HepG2 hepatocytes via AMPK activation, with downstream suppression of the SREBP-1c/FAS lipogenic program [3]

Smilax species:

• No direct AMPK evidence. None of the reviewed Smilax studies measured AMPK signalling. The 2023 claim that sarsaponins potentiate AMPK activation through membrane fluidity modulation had no citation and has been removed.

Nrf2/ARE Pathway Modulation: Antioxidant Defense#

Nrf2 activation is documented for two of the three herbs, with the strongest mechanistic proof again in berberine.

Coptis chinensis (primary, mechanistically proven):

• In LPS-stimulated macrophages and endotoxin-shocked mice, the crosstalk between Nrf2 and AMPK signalling proved important for berberine's anti-inflammatory effect [6]. This is the anchor paper for the AMPK-to-Nrf2 logic of the whole trio concept.
• Downstream induction of antioxidant defenses (the NQO-1/HO-1/GST program is the standard Nrf2 output measured in this literature)

Smilax glabra flavonoids (documented, congeneric):

• S. glabra flavonoid extract activated the Keap1/Nrf2/HO-1 pathway, restored antioxidant enzymes (SOD, glutathione peroxidase, catalase), promoted urinary and renal lead excretion, and suppressed NF-κB-driven IL-1β/IL-6/TNF-α in lead-exposed weaning rats and HEK-293 cells [7]. This is the strongest direct detoxification exemplar in the entire trio literature: 500 years of Chinese use of S. glabra in heavy-metal poisoning, tested in a modern lead model.

Houttuynia cordata (downgraded):

• Fermented, polyphenol-enriched preparations protected keratinocytes against UVA and H₂O₂-induced oxidative stress [4], and ethyl-acetate fractions suppress NF-κB-driven inflammatory output [2]. Direct Nrf2/ARE transcriptional activation has not been demonstrated for H. cordata in the reviewed studies; its antioxidant action is best described as polyphenol ROS scavenging plus NF-κB suppression. The 2023 "primary Nrf2 activator" label has been removed.

NF-κB Pathway Suppression: Anti-inflammatory Control#

Evidence Level: [AN/PR] - Cell studies and mechanistic understanding CONFIDENCE: HIGH for mechanism, LOW for clinical outcomes

All three herbs suppress the NF-κB cascade, at distinct levels, which is the real basis of the complementarity argument.

Coptis chinensis (berberine):

• Anti-inflammatory effect in endotoxin models running through the AMPK-Nrf2 axis [6], with suppression of LPS-induced inflammatory output
• Direct LPS antagonism upstream: berberine acts as a high-affinity LPS antagonist binding the TLR4/MD-2 receptor, established by docking and molecular dynamics simulation [8]

Houttuynia cordata:

• An ethyl-acetate fraction down-regulated NO, PGE₂, TNF-α and IL-6 production and iNOS/COX-2 expression in LPS-stimulated RAW 264.7 macrophages, suppressed NF-κB p65 nuclear translocation, inhibited IκBα phosphorylation, and attenuated p38 and JNK activation [2]

Smilax species (congeneric):

• A flavonoid-enriched S. china root extract (44.3% flavonoids: astilbin, engeletin, isoastilbin, cinchonain Ia, quercetin-3-O-rhamnoside, chlorogenic acid) suppressed protein overexpression of TLR4 and its downstream signal MyD88 in LPS-stimulated macrophages, inhibited xylene-induced ear edema and cotton-ball granuloma in rodents, and reduced TNF-α, COX-2, iNOS, IL-1β and IL-6 [9]
• Steroidal saponins from S. china inhibited COX-2 enzyme activity at 10 µM, with one isolate additionally inhibiting TNF-α production in murine peritoneal macrophages [10]
• S. glabra polysaccharides inhibited pro-inflammatory mediators via the ERK1/2 and JNK pathways in LPS-induced RAW264.7 cells [11]

Note the mechanistic distinction that the 2023 text missed: berberine antagonises LPS at its binding pocket (receptor-level interception), while Smilax flavonoids act by suppressing TLR4 receptor expression itself. Both blunt endotoxin signalling; only the first is "binding".

Pathway Integration and Network Pharmacology#

Evidence Level: [AN] - Cell studies plus pathway analysis; the combination logic itself is theoretical CONFIDENCE: MODERATE for mechanistic complementarity, LOW for clinical validation

Coordinated Network Modulation#

• AMPK-Nrf2 Cross-talk: established for berberine [6]; assumed, not tested, for the other two herbs
• AMPK-NF-κB Antagonism: energy sensing and inflammatory regulation converge, documented in the berberine literature [5,6]
• Nrf2-NF-κB Balance: reciprocal restraint between the antioxidant and inflammatory programs, again documented in the berberine axis [6,7]
• Endotoxin-level interception: berberine's TLR4/MD-2 LPS antagonism [8] sits upstream of the NF-κB suppression that all three herbs display [2,9,11]

Pharmacokinetics: the berberine interaction#

The 2023 section on saponin-enhanced bioavailability has been removed; no reviewed study supports sarsaparilla saponins increasing absorption or inhibiting P-glycoprotein. What the literature does document runs in the opposite direction and is a clinical caution: berberine alters the pharmacokinetics of co-administered CYP3A and P-glycoprotein substrates [12]. For narrow-therapeutic-index drugs in these pathways (digoxin, ciclosporin, tacrolimus as the standard examples), that is an interaction to manage, not an enhancement to exploit.

Individual Botanical Profiles and Mechanistic Actions#

Evidence Level: [AN/PR] - Cell studies, animal research and traditional-use documentation CONFIDENCE: HIGH for mechanisms, MODERATE for therapeutic applications

Coptis chinensis: The Berberine Powerhouse#

Botanical Profile: Coptis chinensis, Chinese goldthread or huanglian, produces golden-yellow rhizomes that are among the richest natural berberine sources, in documented Chinese use for over two thousand years [1].

Primary Bioactive Compounds:

• Berberine (protoberberine alkaloid): AMPK activator [5], Nrf2-crosstalk anti-inflammatory agent [6], TLR4/MD-2 LPS antagonist [8]
• Coptisine, palmatine, epiberberine, jatrorrhizine: the four companion alkaloids identified as the effective anti-MRSA components by spectrum-effect analysis [1]

Molecular Mechanisms:

• AMPK activation with metabolic benefit in diabetic and insulin-resistant states [5]
• AMPK-Nrf2 coupled anti-inflammatory action in endotoxin models [6]
• High-affinity LPS antagonism at the TLR4/MD-2 receptor [8]; in vivo, 40 mg/kg berberine increased survival of Salmonella-challenged mice with no bacteriostatic effect, protection the authors attribute to endotoxin-signalling blockade rather than direct bacterial killing [8]

Therapeutic Applications:

• Metabolic syndrome: AMPK-mediated insulin sensitisation is the best-supported application [5]
• Antimicrobial resistance: ten batches of Rhizoma coptidis showed anti-MRSA activity, including against a norA multidrug-efflux-positive strain, attributed by spectrum-effect analysis to the five protoberberine alkaloids [1]
• Clinical cardiovascular data: a 2023 meta-analysis of 44 RCTs (4,606 patients) found no lipid advantage of berberine alone over routine or statin therapy (TC, TG, LDL-C, HDL-C all non-significant, heterogeneity up to I² = 96%), but did report reductions in hs-CRP, IL-6 and NIHSS stroke scores [13]. Read that as a signal on inflammatory markers, not a lipid drug, with an all-Chinese, high-heterogeneity trial base.

Houttuynia cordata: The Anti-Inflammatory Defender#

Botanical Profile: Houttuynia cordata (fish mint or yuxingcao) is consumed as a vegetable and traditional herb across East Asia, studied as whole-plant extracts, ethyl-acetate fractions and fermented preparations.

Documented actions:

• NF-κB/MAPK suppression: down-regulation of NO, PGE₂, TNF-α, IL-6, iNOS and COX-2 in LPS-stimulated macrophages, with blockade of IκBα phosphorylation, p65 nuclear translocation, and p38/JNK activation [2]
• AMPK engagement (one model): attenuation of hepatic lipid accumulation via AMPK activation in HepG2 cells [3]
• Oxidative-stress cytoprotection: fermented, polyphenol-enriched preparations reduced UVA/H₂O₂-induced damage in keratinocytes [4]
• Immunomodulatory and anti-SARS activity: water extracts showed immunomodulatory and anti-SARS-coronavirus activity in preclinical testing [14]
• Topical antibacterial/anti-inflammatory activity: ethanol extract of Houttuynia poultice showed antibacterial and anti-inflammatory effects [15]

What is downgraded from 2023: direct Nrf2/ARE activation (unproven for this herb), direct TLR4 blockade (not in the reviewed evidence), and specific claims of ACE2/spike-protein binding (removed; the documented antiviral finding is the preclinical anti-SARS activity above [14]).

Smilax species (sarsaparilla): Congeneric Evidence#

Botanical Profile: Commercial sarsaparilla is a mix of S. regelii, S. ornata, S. aristolochiifolia and related species; S. china and S. glabra dominate the mechanistic literature. S. glabra carries 500 years of documented Chinese use in heavy-metal poisoning [7]. The profile below is honest about which species carried which result.

Documented actions:

• Flavonoid extract (S. china): suppressed TLR4 and MyD88 protein overexpression and downstream signalling in LPS-stimulated macrophages, reduced TNF-α, COX-2, iNOS, IL-1β, IL-6, and inhibited acute (xylene ear edema) and chronic (cotton-ball granuloma) inflammation in rodents [9]
• Steroidal saponins (S. china): inhibited COX-2 enzyme activity at 10 µM, with one isolate additionally inhibiting TNF-α production in murine peritoneal macrophages [10]
• Polysaccharides (S. glabra): inhibited pro-inflammatory mediators via ERK1/2 and JNK in LPS-induced macrophages [11]
• Flavonoids (S. glabra) in lead toxicity: activated Keap1/Nrf2/HO-1, restored SOD/glutathione peroxidase/catalase, promoted lead excretion, improved renal function indicators, and suppressed NF-κB-driven IL-1β/IL-6/TNF-α in weaning rats and HEK-293 cells [7]
• S. ornata (Jamaican sarsaparilla): anti-inflammatory and analgesic activity in carrageenan and tail-flick models [16]
• S. glabra rhizome and cancer-cell migration: inhibited migration and invasion of cancer cells via TGF-β pathway suppression in cell studies [17], a congeneric datum, not a clinical indication

What is NOT documented for Smilax: direct LPS binding (the removed 2023 claim; that mechanism belongs to berberine [8]), AMPK activation, and P-glycoprotein inhibition. What the Smilax literature actually shows is down-regulation of the TLR4 receptor complex and its downstream cascades, plus one strong Nrf2/detox exemplar in lead toxicity [7].

Clinical Therapeutic Applications#

Evidence Level: [AN/PP] - Limited human trials, extensive animal research CONFIDENCE: LOW-MODERATE for clinical applications, HIGH for mechanistic rationale

Comprehensive Health Applications#

Specific Protocols and Applications#

Doses below reflect traditional and trial-range practice for the individual herbs. No combination trial of the trio exists; sequencing and pairing suggestions carry LOW confidence.

Metabolic Health Protocol:

• Coptis chinensis (berberine, clinical-trial range): AMPK activation and glucose regulation [5,13]
• Houttuynia cordata (dried herb, traditional tea): anti-inflammatory support [2]
• Smilax species (traditional preparation): anti-inflammatory support (congeneric evidence) [9,11]

Acute Infection Protocol:

• Houttuynia cordata (tea, traditional dose): traditional acute-use herb; preclinical antiviral/immunomodulatory activity [14,15]
• Coptis chinensis (berberine): anti-inflammatory and endotoxin-signalling support [6,8]
• Smilax species (traditional preparation): traditional support

Chronic Inflammation Protocol:

• Smilax species (traditional preparation): anti-inflammatory support (S. china/S. glabra evidence) [9,11,7]
• Coptis chinensis (berberine): NF-κB suppression [6]
• Houttuynia cordata (tea): NF-κB/MAPK suppression [2]

Counter-Evidence & Limitations#

Clinical Evidence Gaps:

• Most evidence is cell culture and animal work; the only substantive clinical dataset is the berberine meta-analysis, and it is negative on lipids [13]
• Bioavailability of oral berberine is low (under 1% in common reporting), a genuine limitation of the Coptis arm
• Species differences may not translate to humans
• No study combines the three herbs; synergy is inferred from overlapping nodes, not measured

Species and Claim Gaps:

• S. regelii, the named third herb, has essentially no dedicated mechanistic literature; the Smilax record here is S. china, S. glabra and S. ornata
• Houttuynia Nrf2 agonism is unproven; antioxidant cytoprotection is the honest description [4]
• Smilax AMPK activation and saponin P-glycoprotein inhibition: no data
• The 2023 version's references: four of five pointed to unrelated papers (a Cyperus osteoclastogenesis study, a wheelchair-rugby supplement survey, an efferocytosis review, and a different SARS-remedy paper); all are replaced here

Safety Concerns:

• Berberine alters pharmacokinetics of CYP3A/P-gp substrates [12]; clinical supervision with digoxin, ciclosporin or tacrolimus-type drugs
• Saponin-rich herbs can cause gastrointestinal irritation at high doses
• Pregnancy and breastfeeding: avoidance rests on absence of data, not documented harm

Evidence Quality Issues:

• Publication bias favouring positive results in Chinese-language journals
• Small samples and heterogeneous extract preparations across studies
• High statistical heterogeneity in the berberine meta-analysis (I² up to 96%) [13]

What the Evidence Doesn't Support:

• Use as sole treatment for serious infections without conventional therapy
• Cancer claims from cell studies [17]
• Any specific synergistic dosing of the trio
• Long-term safety beyond the studied windows

Evidence Summary Table#

Integration with Modern Health Challenges#

Evidence Level: [AN] - Theoretical applications from mechanism CONFIDENCE: LOW for specific clinical applications

Environmental Toxicity Burden:

• S. glabra flavonoids promoted lead excretion with Nrf2-axis restoration in a lead-toxicity model [7]; generalisation beyond lead is untested
• Antioxidant pathway support through the berberine AMPK-Nrf2 axis [6]

Antibiotic Resistance Context:

• Rhizoma coptidis alkaloid mixtures active against MRSA including a norA efflux-positive strain [1]; berberine's in vivo protection operates through endotoxin-signalling blockade rather than bacteriostasis [8]
• These are preclinical findings, not a basis for replacing antibiotics

Metabolic Endotoxemia:

• Berberine's LPS antagonism at TLR4/MD-2 [8] plus NF-κB suppression across all three herbs [2,6,9] gives the trio a coherent story against endotoxin-driven inflammatory load, at the preclinical level

Chronic Viral Conditions:

• Houttuynia's anti-SARS and immunomodulatory activity is preclinical [14]; no human clinical data support antiviral use

Practical Implementation Guidelines#

Evidence Level: [AN] - Clinical practice patterns and pharmacokinetic data CONFIDENCE: MODERATE for safety, LOW for optimal protocols

Administration Strategies#

Optimal Combinations and Timing:

• Traditional dosing splits the three herbs across the day (Coptis with meals, Houttuynia and Smilax as teas or between meals); no pharmacokinetic study validates any specific timing for the combination
• Berberine's absorption is low; the clinically important kinetic fact is the interaction direction - berberine raises exposure of co-administered P-gp/CYP3A substrates [12]

Quality Considerations:

• Standardised extracts (berberine content for Coptis, flavonoid markers for Houttuynia and Smilax) matter more than usual here, because the active fractions differ (alkaloids vs flavonoids vs saponins vs polysaccharides) and determine which mechanism predominates [1,9,10,11]
• Species verification for sarsaparilla material, given the congeneric evidence base

Safety and Contra-indications#

Medical Supervision Required:

• Pregnancy and Lactation: no reproductive-safety data; avoidance is the prudent default (absence of evidence, not documented harm)
• Narrow-therapeutic-index drugs: berberine alters pharmacokinetics of CYP3A/P-gp substrates [12]; supervise digoxin, ciclosporin and tacrolimus-type co-administration
• Diabetes Medications: AMPK activation may add to hypoglycaemic drug effects; monitor

Potential Interactions:

• P-glycoprotein/CYP3A: the documented berberine interaction [12]
• Antibiotics: no formal interaction studies with the trio; do not assume synergy

Future Research Directions#

High-Priority Questions:

• A combination study of the trio (isobologram or combination-index design) - the absence of one is the single biggest gap in this framework
• Direct Smilax regelii pharmacology, versus continued reliance on congeneric species
• Houttuynia Nrf2/ARE assays to settle the plausible-but-unproven arm
• Berberine interaction management in cardiovascular polypharmacy, given the meta-analysis signal on inflammatory markers [13]

References#

All references verified against PubMed at revision (PMIDs given). Four of the five 2023 references pointed to unrelated papers and are not carried forward.

1. Luo JY, Yan D, Yang MH (2014). Study of the anti-MRSA activity of Rhizoma coptidis by chemical fingerprinting and broth microdilution methods. Chinese Journal of Natural Medicines, 12(5), 393-400. PMID 24856764. Full Text

2. Chun JM, et al. (2014). An ethyl acetate fraction derived from Houttuynia cordata extract inhibits the production of inflammatory markers by suppressing NF-κB and MAPK activation in lipopolysaccharide-stimulated RAW 264.7 macrophages. BMC Complementary and Alternative Medicine, 14, 234. PMID 25012519. Full Text

3. Kang H, Koppula S (2014). Houttuynia cordata attenuates lipid accumulation via activation of AMP-activated protein kinase signaling pathway in HepG2 cells. The American Journal of Chinese Medicine, 42(3), 651-664. PMID 24871657. Full Text

4. Kwon N, et al. (2023). Protective Effects of Fermented Houttuynia cordata Against UVA and H₂O₂-Induced Oxidative Stress in Human Skin Keratinocytes. Applied Biochemistry and Biotechnology, 195(5), 3027-3046. PMID 36495375. Full Text

5. Lee YS, et al. (2006). Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes, 55(8), 2256-2264. PMID 16873688. Full Text

6. Mo C, et al. (2014). The crosstalk between Nrf2 and AMPK signal pathways is important for the anti-inflammatory effect of berberine in LPS-stimulated macrophages and endotoxin-shocked mice. Antioxidants & Redox Signaling, 20(4), 574-588. PMID 23875776. Full Text

7. Shi Y, et al. (2020). Protective Effects of Smilax glabra Roxb. Against Lead-Induced Renal Oxidative Stress, Inflammation and Apoptosis in Weaning Rats and HEK-293 Cells. Frontiers in Pharmacology, 11, 556248. PMID 32982754. Full Text

8. Chu M, et al. (2014). Role of berberine in anti-bacterial as a high-affinity LPS antagonist binding to TLR4/MD-2 receptor. BMC Complementary and Alternative Medicine, 14, 89. PMID 24602493. Full Text

9. Feng H, et al. (2020). The flavonoid-enriched extract from the root of Smilax china L. inhibits inflammatory responses via the TLR-4-mediated signaling pathway. Journal of Ethnopharmacology, 256, 112785. PMID 32222576. Full Text

10. Shao B, et al. (2007). Steroidal saponins from Smilax china and their anti-inflammatory activities. Phytochemistry, 68(5), 623-630. PMID 17166529. Full Text

11. Lu CL, et al. (2015). Polysaccharides from Smilax glabra inhibit the pro-inflammatory mediators via ERK1/2 and JNK pathways in LPS-induced RAW264.7 cells. Carbohydrate Polymers, 122, 428-436. PMID 25817687. Full Text

12. Qiu W, et al. (2009). Effect of berberine on the pharmacokinetics of substrates of CYP3A and P-gp. Phytotherapy Research, 23(11), 1553-1558. PMID 19370549. Full Text

13. Yang L, et al. (2023). Efficacy and safety of berberine for several cardiovascular diseases: A systematic review and meta-analysis of randomized controlled trials. Phytomedicine, 112, 154716. PMID 36805484. Full Text

14. Lau KM, et al. (2008). Immunomodulatory and anti-SARS activities of Houttuynia cordata. Journal of Ethnopharmacology, 118(1), 79-85. PMID 18479853. Full Text

15. Sekita Y, et al. (2016). Anti-bacterial and anti-inflammatory effects of ethanol extract from Houttuynia cordata poultice. Bioscience, Biotechnology, and Biochemistry, 80(6), 1205-1213. PMID 27023331. Full Text

16. Khan AK, et al. (2019). Investigation of the anti-inflammatory and the analgesic effects of the extracts from Smilax ornata Lem. (Jamaican sarsaparilla) plant. Journal of Ethnopharmacology, 240, 111830. PMID 31063818. Full Text

17. She T, et al. (2015). Sarsaparilla (Smilax Glabra Rhizome) extract inhibits migration and invasion of cancer cells by suppressing TGF-β1 pathway. PLoS ONE, 10(3), e0118287. PMID 25742000. Full Text