Yunnan Baiyao

• How It Works

  Yunnan Baiyao is a traditional Chinese Medicine formula used for wound healing, as a pain releiver and to stop bleeding. It has not yet been shown to treat cancer.

  Yunnan Baiyao (YNBY; “White medicine from the Province of Yunnan” in Mandarin) is a well-known proprietary traditional Chinese medicine product. The original formula is believed to contain several herbs with notoginseng as the major ingredient. It is promoted as a dietary supplement that can be used both externally and internally to stop bleeding and to treat cancer in humans and in animals. It is also claimed to provide relief from minor aches and pains of muscles and joints associated with backache, arthritis, strains, bruises, sprains, and frostbite.

  Studies done in the lab and in animals show that YNBY and notoginseng have hemostatic, anti-inflammatory and antimicrobial effects. Notoginseng also demonstrated anticoagulant properties.

  Clinical studies suggest that YNBY may be effective in treating bleeding in the uterus, ulcer in the colon and on the skin. It also reduced blood loss during some surgical procedures. Case reports indicate that YNBY reduced bleeding in cancer patients, but it has not been studied as a cancer treatment.

• Purported Uses
  • Stop bleeding
    Clinical studies and case reports show that YNBY is useful in decreasing blood loss during some surgical procedures, and in cancer patients.
  • Relieve pain and bruises
    Although claimed to relieve pain, scientific data are not available to support this use.
  • Arthritis
    YNBY showed anti-inflammatory effects in lab studies. But clinical studies have not been conducted to establish this use in humans.
  • Oral health
    Lab studies show YNBY can reduce the break down of bone tissues. Human studies are needed to confirm this effect.
  • Frostbite
    YNBY may help to bring relief from pain of frostbite and help promote healing. There are no human data to support this claim.
  • Cancer
    YNBY has not been studied as a cancer treatment. Case reports show that YNBY may be useful in decreasing blood loss  in cancer patients.
• Patient Warnings

  This formula may stimulate the growth of hormone-sensitive breast cancer cells.

• Do Not Take If
  • You are taking anticoagulant or antiplatelet drugs: Notoginseng may increase the risk of bleeding when used along with these drugs..
  • You are taking drugs that are substrates of CYP3A: Notoginseng may increase the risk of side effects of these drugs.
  • You are taking drugs that are substrates of CYP1A2, 2E1 substrates: Notoginseng saponins may decrease the effectiveness of these drugs.
  • You are taking drugs that are substrates of Glutathione-S-transferase (GST): Notoginseng may increase the risk of side effects of these drugs.
  • You have a bleeding disorder: YNBY can increase the risk of bleeding.
  • You are pregnant
• Clinical Summary

  Yunnan Baiyao (YNBY; “White medicine from the Province of Yunnan” in Mandarin), is among the well-known proprietary traditional Chinese medicine products. It was formulated a century ago and became a popular remedy for wound healing during the Vietnam War. In the last few decades, the trade name YNBY has been expanded into a product line that includes pills, tincture, and toothpaste. The original formula is believed to contain multiple herbs with notoginseng as the main ingredient. It is also promoted as a dietary supplement that can be used both externally and internally to stop bleeding and to treat cancer in humans and in animals. Other claims include relief from minor aches and pains of muscles and joints associated with backache, arthritis, strains, bruises, sprains, and frostbite ⁽¹⁾.

  In vitro and animal studies indicate that YNBY and notoginseng have hemostatic ^{(2) (3) (4) (5)}, anti-inflammatory ^{(8) (9) (10) (11) (12)} and antimicrobial ⁽⁵⁾ effects. Notoginseng by itself demonstrated anticoagulant, antiplatelet ⁽⁶⁾, and fibrinolytic ⁽⁷⁾ activities.

  Clinical studies suggest that YNBY may be effective in treating uterine hemorrhage, ulcerative colitis and skin ulcers ⁽¹³⁾. It also reduced intraoperative blood loss during transurethral resection of prostate ⁽¹⁴⁾ and during oral surgery ⁽¹⁵⁾. Case reports indicate that YNBY reduced bleeding in cancer patients ⁽²⁹⁾. But YNBY has not been studied as a cancer treatment.

  Ginsenosides derived from notoginseng were shown to exert estrogenic effects ⁽¹⁶⁾, and may stimulate the growth of hormone-sensitive breast cancer cells ^(17) (18).

• Purported Uses
  • Stop bleeding
  • Relieve pain
  • Wound healing
  • Arthritis
  • Oral health
  • Frostbite
  • Cancer
• Mechanism of Action

  YNBY demonstrates hemostatic effects when applied topically on open wounds ⁽²⁾. Microscopic examination identified nanofiber components in YNBY which may help to activate blood clotting. This carbon-based nanofiber also acts as a scaffolding for tissue repair and prevents infection by sealing up the wound ⁽⁴⁾.

  An in vitro study on the wound-healing effects of YNBY suggests anti-inflammatory activity through suppression of lymphocyte growth and expression of pro-inflammatory cytokines ⁽¹¹⁾.  Another study showed modulation of COX and LOX pathways ⁽³⁰⁾. YNBY extract may be useful for rheumatoid arthritis by activating intracellular prostaglandin E(2) and thromboxane B(2) in osteoblasts ⁽⁸⁾.

  When taken internally, YNBY can improve circulation and reduce swelling and bruises. The effects may be due to the anticoagulant and antiplatelet effects ⁽⁶⁾ exerted systemically by notoginseng via reduction of fibrinogen in blood ⁽⁷⁾. Notoginseng also was found to protect endothelial function ⁽¹⁹⁾ and vascular integrity by regulating Focal Adhesion Kinase (FAK), integrin expression and NF-kappa B functions ⁽²⁰⁾; and to inhibit vascular intimal hyperplasia by lowering the expression of Proliferating Cell Nuclear Antigen (PCNA), cyclinE, cyclinD1, FN and MMP-9. ⁽²¹⁾.

  YNBY also showed antimicrobial activity. In a Pseudomonas aeruginosa model, a water extract of YNBY reduced bacterial virulence by affecting the quorum-sensing (QS) signaling circuit and by reducing the formation of biofilm ⁽⁵⁾.

  In other studies, notoginsenoside Ft1, a saponin constituent of notoginseng, induced platelet aggregation by binding to platelet P2Y₁₂ receptors ⁽³⁾. It demonstrated anti-inflammatory effects by inhibiting neutrophil function and NO and PGE2 production, through reduced expression of iNOS and COX-2 ⁽¹⁰⁾. A study conducted on peritoneal macrophages found that notoginseng inhibits COX-2 expression at an early stage, elevating it at a later stage ⁽²²⁾. Data also suggest it can inhibit expression of NF-kappaB activity and TNF-alpha mRNA ⁽¹²⁾. Notoginseng may play a role in the treatment of periodontal diseases by suppressing MMP-2 expression and by inhibiting breakdown of bone tissue ⁽⁹⁾. In another study, Ginsenoside-Rd, isolated from notoginseng, has been shown to reduce atherosclerosis by inhibiting LDL uptake and cholesterol accumulation in macrophages ⁽²³⁾.

  Some studies report that notoginseng and the constituent ginsenosides mimic estrogen ⁽¹⁶⁾ by binding and activating the estrogen receptor ⁽¹⁸⁾ and ER-alpha pathway ⁽¹⁷⁾. In an animal study, notoginseng selectively sensitized tumor cells to radiation ⁽²⁴⁾. However, this effect has not been demonstrated in humans.

• Warnings

  May stimulate the growth of hormone-sensitive breast cancer ⁽¹⁶⁾

• Contraindications
  • Bleeding disorders
  • Pregnant women should not consume this formula.
• Herb-Drug Interactions
  • Anticoagulant or antiplatelet drugs: Notoginseng has anticoagulant, antiplatelet ⁽⁶⁾, and fibrinolytic ⁽⁷⁾ activities, and may increase the risk of bleeding when used with these drugs.
  • CYP3A substrates: Notoginseng saponins can inhibit CYP3A activity and may affect the metabolism of substrate drugs ⁽²⁵⁾.
  • CYP1A2, 2E1 substrates: Notoginseng saponins can induce CYP1A2 and may affect the metabolism of substrate drugs ^(26) (27).
  • Glutathione-S-transferase (GST) substrates: Notoginseng inhibits the glutathione-S-transferase activity and may interfere with the metabolism of substrate drugs ⁽²⁸⁾.
• Herb Lab Interactions

  May increase PT, PTT, INR.

• References

  1. Food and Drug Administration. Correspondence with Manufacturer; 2002.

  2. Fan C, Song J, White CM. A comparison of the hemostatic effects of notoginseng and yun nan bai yao to placebo control. J Herb Pharmacother. 2005;5:1-5.

  3. Gao B, Huang L, Liu H, et al. Platelet P2Y(1)(2) receptors are involved in the haemostatic effect of notoginsenoside Ft1, a saponin isolated from Panax notoginseng. Br J Pharmacol. 2014;171:214-223. doi: 10.1111/bph.12435

  4. Lenaghan SC, Xia L, Zhang M. Identification of nanofibers in the Chinese herbal medicine: Yunnan Baiyao. J Biomed Nanotechnol. 2009;5:472-476.

  5. Zhao ZG, Yan SS, Yu YM, et al. An aqueous extract of Yunnan Baiyao inhibits the quorum-sensing-related virulence of Pseudomonas aeruginosa. J Microbiol. 2013;51:207-212. doi: 10.1007/s12275-013-2595-x

  6. Lau AJ, Toh DF, Chua TK, Pang YK, Woo SO, Koh HL. Antiplatelet and anticoagulant effects of Panax notoginseng: comparison of raw and steamed Panax notoginseng with Panax ginseng and Panax quinquefolium. J Ethnopharmacol. 2009;125:380-386. doi: 10.1016/j.jep.2009.07.038

  7. Cicero AF, Vitale G, Savino G, Arletti R. Panax notoginseng (Burk.) effects on fibrinogen and lipid plasma level in rats fed on a high-fat diet. Phytother Res. 2003;17:174-178. doi: 10.1002/ptr.1262

  8. He H, Ren X, Wang X, et al. Therapeutic effect of Yunnan Baiyao on rheumatoid arthritis was partially due to regulating arachidonic acid metabolism in osteoblasts. J Pharm Biomed Anal. 2012;59:130-137. doi: 10.1016/j.jpba.2011.10.019

  9. Jang YJ, Kim ME, Ko SY. n-Butanol extracts of Panax notoginseng suppress LPS-induced MMP-2 expression in periodontal ligament fibroblasts and inhibit osteoclastogenesis by suppressing MAPK in LPS-activated RAW264.7 cells. Arch Oral Biol. 2011;56:1319-1327. doi: 10.1016/j.archoralbio.2011.05.010

  10. Jin UH, Park SG, Suh SJ, et al. Inhibitory effect of Panax notoginseng on nitric oxide synthase, cyclo-oxygenase-2 and neutrophil functions. Phytother Res. 2007;21:142-148. doi: 10.1002/ptr.2018

  11. Li R, Alex P, Ye M, Zhang T, Liu L, Li X. An old herbal medicine with a potentially new therapeutic application in inflammatory bowel disease. Int J Clin Exp Med. 2011;4:309-319.

  12. Wang Y, Peng D, Huang W, Zhou X, Liu J, Fang Y. Mechanism of altered TNF-alpha expression by macrophage and the modulatory effect of Panax notoginseng saponins in scald mice. Burns. 2006;32:846-852. doi: 10.1016/j.burns.2006.02.001

  13. Yang B, Xu ZQ, Zhang H, et al. The efficacy of Yunnan Baiyao on haemostasis and antiulcer: a systematic review and meta-analysis of randomized controlled trials. Int J Clin Exp Med. 2014;7:461-482.

  14. Li NC, Pan BN, Wang HJ, et al. [The effect of Yunnan Baiyao on reduction of intra-operative bleeding of the patients undergoing transurethral resection of prostate]. Zhonghua Yi Xue Za Zhi. 2007;87:1017-1020.

  15. Tang ZL, Wang X, Yi B, Li ZL, Liang C, Wang XX. [Prophylactic administration of Yunnan Baiyao capsule reduces intra-operative blood loss in orthognathic surgery]. Zhonghua Kou Qiang Yi Xue Za Zhi. 2008;43:542-545.

  16. Chan RY, Chen WF, Dong A, Guo D, Wong MS. Estrogen-like activity of ginsenoside Rg1 derived from Panax notoginseng. J Clin Endocrinol Metab. 2002;87:3691-3695. doi: 10.1210/jcem.87.8.8717

  17. Lau WS, Chan RY, Guo DA, Wong MS. Ginsenoside Rg1 exerts estrogen-like activities via ligand-independent activation of ERalpha pathway. J Steroid Biochem Mol Biol. 2008;108:64-71. doi: 10.1016/j.jsbmb.2007.06.005

  18. Lee YJ, Jin YR, Lim WC, et al. Ginsenoside-Rb1 acts as a weak phytoestrogen in MCF-7 human breast cancer cells. Arch Pharm Res. 2003;26:58-63.

  19. Lin F, Gou X. Panax notoginseng saponins improve the erectile dysfunction in diabetic rats by protecting the endothelial function of the penile corpus cavernosum. Int J Impot Res. 2013;25:206-211. doi: 10.1038/ijir.2013.19

  20. Yuan Z, Liao Y, Tian G, et al. Panax notoginseng saponins inhibit Zymosan A induced atherosclerosis by suppressing integrin expression, FAK activation and NF-kappaB translocation. J Ethnopharmacol. 2011;138:150-155. doi: 10.1016/j.jep.2011.08.066

  21. Wu L, Zhang W, Tang YH, et al. Effect of total saponins of “panax notoginseng root” on aortic intimal hyperplasia and the expressions of cell cycle protein and extracellular matrix in rats. Phytomedicine. 2010;17:233-240. doi: 10.1016/j.phymed.2009.07.021

  22. Yuan ZB, Zhang HG, Jia Y, Cheng YQ, Li XH. Temporal expression of cyclooxygenase-2 in peritoneal macrophages of rats and effects of panax notoginseng saponins. Inflamm Res. 2009;58:74-80. doi: 10.1007/s00011-009-8044-y

  23. Li J, Xie ZZ, Tang YB, Zhou JG, Guan YY. Ginsenoside-Rd, a purified component from panax notoginseng saponins, prevents atherosclerosis in apoE knockout mice. Eur J Pharmacol. 2011;652:104-110. doi: 10.1016/j.ejphar.2010.11.017

  24. Chen FD, Wu MC, Wang HE, et al. Sensitization of a tumor, but not normal tissue, to the cytotoxic effect of ionizing radiation using Panax notoginseng extract. Am J Chin Med. 2001;29:517-524. doi: 10.1142/s0192415x0100054x

  25. Yang ZM, Yang XF. [Inhibitory effect of PNS on drug metabolism enzyme CYP3A in rat livers and its kinetic analysis]. Zhongguo Zhong Yao Za Zhi. 2012;37:3486-3489.

  26. Liu R, Qin M, Hang P, Liu Y, Zhang Z, Liu G. Effects of Panax notoginseng saponins on the activities of CYP1A2, CYP2C9, CYP2D6 and CYP3A4 in rats in vivo. Phytother Res. 2012;26:1113-1118. doi: 10.1002/ptr.3688

  27. Chen YJ, Wang YG, Ma ZC, et al. [Effect of Panax notoginseng saponins on liver drug metablic enzyme activity, mRNA and protein expressions in rats]. Zhongguo Zhong Yao Za Zhi. 2014;39:3824-3828.

  28. Yang Z, Yang X. [Inhibition of glutathione-S-transferase by total saponins of Panax notoginseng and its kinetics analysis in liver of mice]. Zhongguo Zhong Yao Za Zhi. 2011;36:2413-2417.

  29. Ladas EJ, Karlik JB, Rooney D, et al. Topical Yunnan Baiyao administration as an adjunctive therapy for bleeding complications in adolescents with advanced cancer. Support Care Cancer. 2012 Dec;20(12):3379-83. doi: 10.1007/s00520-012-1598-1.

  30. Ren X, Zhang M, Chen L, et al. The anti-inflammatory effects of Yunnan Baiyao are involved in regulation of the phospholipase A2/arachidonic acid metabolites pathways in acute inflammation rat model. Mol Med Rep. 2017 Oct;16(4):4045-4053. doi: 10.3892/mmr.2017.7104.