Can Traditional Herbal Medicine Help Heal Chronic Diabetic Foot Ulcers?

Pages: 16 - 20
Alexander M. Reyzelman, DPM, and Irina Bazarov, MS

Despite the multitude of wound healing products and technologies that have come out in recent years, the treatment of chronic diabetic ulcers still remains a challenge. An evolving scientific understanding of wound physiology has led to the introduction of new wound care products targeting specific wound healing abnormalities.

   Unfortunately, the complexity of imbalances responsible for delayed wound healing makes it extremely difficult to develop a single best wound care product. More often than not, podiatrists have to resort to the use of an assortment of skin substitutes, topical and oral antibiotics, and various expensive dressings. Not only are the results of this treatment strategy often less than optimal, the use of multiple treatment modalities also contributes to the staggering cost of diabetic wound care.1

   In the last few decades, the increasing popularity of herbal therapy has led wound care specialists to turn to common botanicals in the hope of finding a more effective and less costly product for healing of chronic wounds.2

   Herbal medicine has been in use successfully to treat various dermatological conditions for thousands of years. Honey and aloe vera extracts are some of the most popular natural products currently used in topical wound care in the United States. The wound healing properties of honey are attributed to the antimicrobial, anti-inflammatory and antioxidant qualities of catalase and flavonoids, and are well established in current medical practice.3,4 Aloe vera possesses potent anti-inflammatory and analgesic properties due to its inhibitory action on thromboxane A2 and B2, prostaglandin 2a and bradykinin. Research has shown aloe vera to promote healing of radiation-damaged skin and pressure ulcers.5,6

Examining The Increasing Prevalence Of Herbal Therapy

Traditional Chinese herbal medicine has been gaining increasing interest around the world. While conventional Western medicine is based on the principle of finding the most specific agent to target a single biomolecule or biochemical signal transduction pathway, traditional Chinese herbal medicine uses a combination of multiple herbs, each of which possesses distinctive properties but acts synergistically to influence many targets throughout the body.7

   While herbal medicine has been in practice for nearly 4,000 years in China and its uses have been extensively documented in Chinese clinical literature, it was largely unfamiliar to Western clinicians until the 1980s. Western physicians initially demonstrated the efficacy of Chinese herbal medicine in a double-blind, placebo-controlled study on children with atopic dermatitis in England.8 The study lasted for five months and included 47 children, who took an oral preparation of either a specially selected combination of 10 Chinese medicinal herbs or a mixture of similarly tasting but randomly combined herbs. The study authors noted that patients treated with herbal medicine showed significantly higher improvement in erythema and surface lesions in comparison to the patients treated with placebo.

   Following the success of the aforementioned study, researchers and clinicians have assessed traditional Chinese herbal medicine for a variety of conditions in the U.S. and Europe, and there is now a high volume of English-language scientific literature.

A Closer Look At A Novel Healing Ointment

One recent addition to the arsenal of traditional Chinese herbal medicine-based therapies available to Western physicians is a topical ointment, WinVivo Healing Balm (WinVivo Corp.), which we have used successfully to treat difficult-to-heal lower extremity ulcers.9 WinVivo has 11 ingredients, which include camellia oil and extracts of tree peony bark, coptis root, rhubarb root, fritillaria bulb, lithospermum root, chicken gizzard, and corydalis rhizome, as well as dragon’s blood resin, borneol powder and bone ash. The ointment has been in use to treat acute and chronic wounds. Randomized clinical studies in China have shown it to be effective in the healing of second- and third-degree burns.10

   A number of ingredients included in WinVivo ointment exhibit properties that could be beneficial in wound healing.

   Tree peony bark (Paeonia suffruticosa) has been part of traditional Chinese medicine since the 1st century AD. It contains several compounds with analgesic, antioxidant and antipyretic properties.11 The anti-inflammatory effects of tree peony are theoretically due to the suppression of the pro-inflammatory cytokines TNF-a and IL-6, and modulation of the phosphorylation of mitogen-activated protein kinase (MAPK) cascade.12 Since prolonged, out of control inflammatory response is believed to be one of the major mechanisms responsible for the failure of chronic wounds to heal, the plant’s anti-inflammatory properties could potentially facilitate the progression of wounds to faster healing.13

   Coptis root (Coptis chinensis) is a rich source of berberine alkaloids, which are well known for their anti-cancer, antimicrobial and anti-inflammatory effects. In vitro and in vivo studies have shown that the plant possesses a broad spectrum of antibacterial, antifungal and antiviral activity.14-16 A recent study in mice with irritable bowel syndrome has demonstrated that coptis root has potent analgesic properties that are likely due to an inhibitory effect on serotonin release and pain transmission.17

   Rhubarb root (Rheum palmatum) has been recognized as a medicinal plant for thousands of years and now grows around the world. Its main active compound, emodin, is well known for its antimicrobial and anti-inflammatory properties. A recent in vitro study has demonstrated that emodin inhibits proliferation of pro-inflammatory cytokines TNF-a, IL-1b, IL-6 and IL-8, as well as prostaglandin E2 and matrix-metalloproteinases (MMP) 1 and MMP-13.18 In addition, in vivo investigation has revealed that topical application of emodin promotes healing of excisional wounds in rats by regulating the SMAD-mediated TGF-β1 signaling pathway.19

   Research has shown that lithospermum root (Lithospermum erythrorhizon) and its major component shikonin reduce inflammation by inhibiting signaling pathways leading to activation of AP-1 and NF-kB transcription factors in macrophages.20 Shikonin derivatives from lithospermum root possess antifungal, antiviral and antibacterial properties.21,22 In addition, lithospermum root may act as an antioxidant.23 Fujita and colleagues have demonstrated that an extract of lithospermum root accelerates wound healing in diabetic mice by shortening of the inflammatory phase and advancement of proliferative and maturation phases.24

   Corydalis tuber (Corydalis turtschaninovii) has been in use in traditional Chinese medicine since the 8th century AD. One of its components, dehydrocorydaline, possesses potent anti-inflammatory properties due to its role in inhibiting antigen-induced histamine release.25,26 One study demonstrated that pseudocoptisine, another compound obtained from corydalis, reduces levels of pro-inflammatory mediators iNOS, COX-2 and TNF-a through inhibition of NF-kB and suppression of ERK and p38 phosphorylation.27

Pertinent Case Studies In Diabetic Wound Care

Below are two clinical cases of successful WinVivo wound ointment use that are representative of the results we typically obtain in our practice. Both patients suffered from severe microvascular complications of longstanding type 2 diabetes mellitus and had chronic, non-healing neuropathic foot ulcers that were recalcitrant to standard wound therapies. In both cases, short-term treatment with WinVivo wound ointment appeared to reverse the stalled healing process by decreasing inflammation and promoting epithelialization and contraction of the wound.

   A 69-year-old male presented to our clinic with an infected neuropathic ulcer on the dorsum of his forefoot. The patient had a past medical history of poorly controlled type 2 diabetes, congestive heart failure and severe leg edema. The ulcer has likely originated secondary to shoe irritation.

   Following debridement of necrotic tissue, the patient started on IV antibiotics and negative pressure wound therapy (NPWT) for two months. After some improvement in wound size, we ceased using NPWT and started the patient on WinVivo. We saw the patient in clinic weekly, assessed the wound and applied the wound ointment at each visit and every three days thereafter via home healthcare. We dressed the wound with sterile gauze and a Jones compression dressing.

   After two months of WinVivo application, the wound demonstrated an increase in granulation tissue formation and decreased amounts of exudate, biofilm and malodor. Since starting WinVivo treatment, the percentage of wound closure, estimated as the change in wound area relative to initial wound size, was 94 percent.

   The second patient is a 50-year-old male, who had undergone a transmetatarsal amputation due to a progressive foot infection. He presented to our clinic with a non-healing ulcer at his distal forefoot stump following surgical wound dehiscence and a series of unsuccessful skin graft applications. After a revision of the transmetatarsal amputation, the patient started on NPWT for two months.

   After stopping NPWT, we began treating him with topical WinVivo applications. The patient applied the wound ointment at home daily and presented to the clinic weekly for follow-up. After 3.5 months of treatment with WinVivo, the wound exhibited significant size reduction as well as a decreased amount of exudate, malodor and peri-ulcer erythema. The percentage of wound closure since the start of WinVivo treatment was 91 percent.

In Conclusion

WinVivo Healing Balm is a promising new topical treatment for chronic diabetic foot ulcers. By combining several traditional Chinese medicinal herbs in one formulation, WinVivo offers benefits of anti-inflammatory, antioxidant, antimicrobial and analgesic properties. These properties simultaneously address the complex issues that occur in chronic wounds. The unique combination in this product is something we have not seen in other wound care products available today. WinVivo clearly deserves a closer look as a valid alternative to more expensive treatments currently on the market.

   Dr. Reyzelman is an Associate Professor in the Department of Medicine at California School of Podiatric Medicine at Samuel Merritt University in Oakland, Calif. He is the Co-Director of the University of California, San Francisco Center for Limb Preservation.

   Ms. Bazarov is a fourth-year student at the California School of Podiatric Medicine at Samuel Merritt University in Oakland, Calif.

1. Driver VR, Fabbi M, Lavery LA, Gibbons G. The costs of diabetic foot: The economic case for the limb salvage team. J Vasc Surg. 2010; 52(3 Suppl):17S-22S.
2. Kumar B, Vijayakumar M, Govindarajan R, Pushpangadan P. Ethnopharmacological approaches to wound healing--exploring medicinal plants of india. J Ethnopharmacol. 2007; 114(2):103-113.
3. Davis SC, Perez R. Cosmeceuticals and natural products: Wound healing. Clin Dermatol. 2009; 27(5):502-506.
4. Molan PC. The evidence supporting the use of honey as a wound dressing. Int J Low Extrem Wounds. 2006; 5(1):40-54.
5. Roberts DB, Travis EL. Acemannan-containing wound dressing gel reduces radiation-induced skin reactions in C3H mice. Int J Radiat Oncol Biol Phys. 1995; 32(4):1047-1052.
6. Thomas DR, Goode PS, LaMaster K, Tennyson T. Acemannan hydrogel dressing versus saline dressing for pressure ulcers. A randomized, controlled trial. Adv Wound Care. 1998; 11(6):273-276.
7. Koo J, Desai R. Traditional Chinese medicine in dermatology. Dermatol Ther. 2003; 16(2):98-105.
8. Sheehan MP, Atherton DJ. A controlled trial of traditional chinese medicinal plants in widespread non-exudative atopic eczema. Br J Dermatol. 1992; 126(2):179-184.
9. Reyzelman A, Bazarov I. Initial clinical assessment of a novel multifunctional topical ointment for difficult-to-heal wounds: A case series. Adv Skin Wound Care. 2012; In press.
10. Xiong GM, Li JM, Xiong WJ. Study on puji ointment in treating 628 cases with second and third-degree burns and its decrustative effect. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1994; 14(7):415-417.
11. Ding HY, Chou TH, Lin RJ, et al. Antioxidant and antimelanogenic behaviors of paeonia suffruticosa. Plant Foods Hum Nutr. 2011; 66(3):275-284.
12. Wu M, Gu Z. Screening of bioactive compounds from moutan cortex and their anti-inflammatory activities in rat synoviocytes. Evid Based Complement Alternat Med. 2009; 6(1):57-63.
13. Menke NB, Ward KR, Witten TM, Bonchev DG, Diegelmann RF. Impaired wound healing. Clin Dermatol. 2007; 25(1):19-25.
14. Yan H, Sun X, Sun S, et al. Anti-ultraviolet radiation effects of coptis chinensis and phellodendron amurense glycans by immunomodulating and inhibiting oxidative injury. Int J Biol Macromol. 2011; 48(5):720-725.
15. Wei GX, Xu X, Wu CD. In vitro synergism between berberine and miconazole against planktonic and biofilm candida cultures. Arch Oral Biol. 2011; 56(6):565-572.
16. Wu Y, Li JQ, Kim YJ, Wu J, Wang Q, Hao Y. In vivo and in vitro antiviral effects of berberine on influenza virus. Chin J Integr Med. 2011; 17(6):444-452.
17. Tjong Y, Ip S, Lao L, et al. Analgesic effect of coptis chinensis rhizomes (coptidis rhizoma) extract on rat model of irritable bowel syndrome. J Ethnopharmacol. 2011; 135(3):754-761.
18. Ha MK, Song YH, Jeong SJ, et al. Emodin inhibits proinflammatory responses and inactivates histone deacetylase 1 in hypoxic rheumatoid synoviocytes. Biol Pharm Bull. 2011; 34(9):1432-1437.
19. Tang T, Yin L, Yang J, Shan G. Emodin, an anthraquinone derivative from rheum officinale baill, enhances cutaneous wound healing in rats. Eur J Pharmacol. 2007; 567(3):177-185.
20. Kim H, Kim J, Park J, et al. Water extract of gromwell (lithospermum erythrorhizon) enhances migration of human keratinocytes and dermal fibroblasts with increased lipid synthesis in an in vitro wound scratch model. Skin Pharmacol Physiol. 2011; 25(2):57-64.
21. Brigham LA, Michaels PJ, Flores HE. Cell-specific production and antimicrobial activity of naphthoquinones in roots of lithospermum erythrorhizon. Plant Physiol. 1999; 119(2):417-428.
22. Gao H, Liu L, Qu ZY, et al. Anti-adenovirus activities of shikonin, a component of chinese herbal medicine in vitro. Biol Pharm Bull. 2011; 34(2):197-202.
23. Wang Z, Liu T, Gan L, et al. Shikonin protects mouse brain against cerebral ischemia/reperfusion injury through its antioxidant activity. Eur J Pharmacol. 2010; 643(2-3):211-217.
24. Fujita N, Sakaguchi I, Kobayashi H, et al. An extract of the root of lithospermun erythrorhison accelerates wound healing in diabetic mice. Biol Pharm Bull. 2003; 26(3):329-335.
25. Kubo M, Matsuda H, Tokuoka K, Ma S, Shiomoto H. Anti-inflammatory activities of methanolic extract and alkaloidal components from corydalis tuber. Biol Pharm Bull. 1994; 17(2):262-265.
26. Matsuda H, Tokuoka K, Wu J, et al. Inhibitory effects of dehydrocorydaline isolated from corydalis tuber against type I-IV allergic models. Biol Pharm Bull. 1997; 20(4):431-434.
27. Yun KJ, Shin JS, Choi JH, et al. Quaternary alkaloid, pseudocoptisine isolated from tubers of corydalis turtschaninovi inhibits LPS-induced nitric oxide, PGE(2), and pro-inflammatory cytokines production via the down-regulation of NF-kappaB in RAW 264.7 murine macrophage cells. Int Immunopharmacol. 2009; 9(11):1323-1331.

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