Chinese Medicine promotes Wound Healing

 Frank Li   July 29 2012

https://frankwaterloo.wordpress.com/2016/01/27/chinese-medicine-on-wound-healing/

In Western medicine, the suture removal after laparotomy conventionally needs to wait for healing 1 week or more. However, it is only needs 1 or 2 days if treated by Chinese drugs.

The incision fat liquefaction is a thorny problem clinically in Western medicine, even causing death. However, the one on hip incision of hipbone fracture was being healed to crust in hours by sprinkling hammered rough powder from crude Chinese herbs’ slices without sterilization.

   Many successful cases have been demonstrated that Chinese drugs have magic curative effect on chronic refractory wounds or ulcers. 

   The unique potence comes from potentiating synergistic effects of multiple bioactive constituents of compound Chinese drugs. 

   The facts have subverted the conventional process of wounds healing. Chinese drugs provided a new effective and cheaper approach for wounds treatment especially for the chronic refractory one. Obviously, it has promising market potential. 

Introduction

2. Effects of Chinese drugs on wounds healing

2.1. Restoration of wound blood circulation

2.2. The number and function of immune cells

2.3. Wound fibronectin (Fn)

2.4. Basic fibroblast growth factor (bFGF)

2.5. Collagen synthesis and metabolism

2.6. Wound nutritional status

2.7. Acidification wound

2.8. Granulation tissue cells’ proliferation and fibroblasts’ function

2.9. Wound contraction materials

2.10. Health beneficial wound pus’ secretion

2.11. Original shape and color’s restoration

2.12. Bacteriostasis

2.13. Promote the recovery of bone fractures

2.13.1. Reconstruction of blood circulation system

2.13.2. Promotion of calcium deposition and enhance the callus quality

2.13.3. Promotion of growth hormone secretory

3.13.4. Increase of the level of bone morphogenetic protein

2.13.5. Promotion of the TGF-β secretion of osteoblast

2.13.6. The generation of IGF-1

 Introduction 

In the United States, deadly mystery superbugs kills soldiers and causes to amputate limbs among troops wounded in Iraq [1][2][3][4][5]. Some of them developed only from a slight wound. Because have no effective antibiotics against mystery super bugs – Acinetobacter baumannii.

 Until now there is no report that the infections of Acinetobacter baumannii are being controlled. The main reason maybe is that the Acinetobacter baumannii can mutate and update continuously to resist any grade of antibiotics, because those antibiotics even act as triggers or parts for the bacterial mutation. Maybe, human beings will never win in fighting against the bacteria by antagonizing approach.

Currently, Western medicine treats the wounds mainly by surface disinfection, suture and intravenous antibiotics. The process of wounds repairing normally goes through the following phases:

1.Inflammatory Phase, it lasts about 24 hours, 2. Proliferation Phase, it lasts from 24 to 72 hours. 3.Fibroblastic Phase, it lasts from 15 to 20 days. 4. Maturation Phase, it lasts up to one year.

According to the theory of Western medicine, inflammatory response is an integral part in wound healing. Early inhibition of inflammatory response will delay the wound healing. Intensive inflammatory response will significantly speed up the wounds healing.

The normal days of the suture removal after surgery are as following: Eyes 3-4, Face 4-5, Neck 4-5, Scalp 7, Trunk 6-14, Joint 14 and Hand & Foot 10-21.

Above process of wounds treatment and healing are in normal situation. Indeed there are many abnormal situation clinically. Such as the mystery super bugs kill US soldiers. Some chronic ulcers and incision fat liquefaction, etc.

There were various types of growth factors have been applied in wounds treatment. Such as epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), etc.

However, the clinical effects were not satisfied. It was mainly because of there are large number of protease exists including metalloproteinases in the chronic refractory wound, which will break down the growth factor of endogenous and exogenous. Thus lead wound healing slowed down or even stopped. In addition, the content of interleukin-8 (IL-8) and interleukin-10 (IL-10) is higher in the form of autocrine to inhibit the tissue’s repairing, weaken the collagen synthesis, and increase the cell apoptosis.

Therefore, we need to change the way of thinking in combating with the bacteria from the level of philosophy. That is from reductionism to holism, from antagonize to immune regulation, from killing the infectious bugs by updating the antibiotics to defeating them by enhancing human immunity.

For thousands years, Chinese medicine has developed unique therapeutic approaches on wound treatment by natural drugs. Along with the development of modern biotechnology, their therapeutic mechanism has been revealed gradually. Such as: restoring the blood circulation, improving the immune function, increasing fibronectin, increasing basic fibroblast growth factor, enhancing the collagen synthesis and metabolism, improving the nutritional status, acidification wounds, promoting the granulation tissue cells proliferation, improving the fibroblasts function, increasing the wound contraction materials, etc.

Following is a case that happened 10 years ago.

1998, my younger brother hipbone fractured in a car accident. After one week of hip operation there was still 50 mm unhealed on 300 mm incision suture and happened fat liquefaction due to doctor forgot putting a surgical drainage tube. Besides the replacement of medical gauze and adjustment of the intravenous antibiotics conventionally, the doctors did not give more help.

I worried about the wound infection or necrosis, so bought some crude Chinese herbs’ slices and hammered them into coarse powder, then sprinkling on the incision watering area directly without sterilization. After 3 hours when I opened the covered-gauze found that the unhealed incision has crusted entirely. The appearance showed that the crust formed much earlier than 3 hours. The Chinese herbs’ effect surprised me very much. Because that the incision fat liquefaction is difficult to be healed, it needs to use Infra-red radiation or insulin, etc. Some time, it may lead to serious consequences, such as, the symptoms of systemic poisoning.

I have been worrying for that the wound watering outlet was being blocked too quickly. However, until now, more than 10 years has past without any sequel.

 June，2003，I had my younger brother taken the photo on the area of incision suture as above.

From above experience, I have aroused an idea that sprinkle the Chinese drugs powder on the wound immediately after operation or injured to promote the wound crusted as faster as possible, so that avoid the infections. For those needs further treatment will be helpful from not being infected before getting suitable operation. 

Normally the laparotomy suture removal after operation needs waiting for healing 1 week or more. However, there was report that only needs 1 or 2 days if treated by Chinese drugs, and my younger brother’s fat liquefaction of hip incision being healed only in hours. The facts lead to guess that Chinese drugs might have changed the recognized healing process of wounds, that is immediately goes into the proliferative phase by weakening or avoiding the phase of inflammatory response. Simultaneity, this mixed healing process is also being speeded up largely by supplying enough nutrients, which are the essential for wounds healing. Although I did not find any report on this yet, however, according to being unbelievable shortened heeling process and the medicinal and nutritional properties of Chinese drugs, this is a unique logical explanation. 

Chinese drugs have demonstrated magic therapeutic effect on chronic refractory wounds or ulcers. 

I believe that Chinese drugs can treat the infections of Acinetobacter baumannii to avoid being amputated. It is by destroying Acinetobacter baumannii’s living environment by accelerating healing to inhibit inflammatory rather than by killing Acinetobacter baumannii directly.

On other hands, the therapeutic constituents of Chinese drugs would permeate into the patient’s body through the blood vessels in wound area to take the effect from external to internal. It can enhance the health condition and immunity overall. Also it can help reducing the psychological stress caused by injury and speed up the wounds healing. 

According to the current biological research results for the Chinese drugs and principle of compound prescription of Chinese medicine, it is possible to realize the scarless healing and restore the original appearance for the sake of beauty in a safe and faster way. 

In China, there is a Yunnan Baiyao as family essential drugs for a long time. As a powder, it is convenient and wonderful in wound hemostasis and healing by sprinkling on the surface of the wounds without disinfection treatment. However, it is less than ideal in healing time and scarless. 

Now, let’s look at the therapeutic mechanism of Chinese drugs on wounds.

2. Effects of Chinese drugs on wounds healing 

2.1. Restoration of wound blood circulation

Artery ischemia, intravenous blood-sludging and partial denervation or neuropathy is the important reason that delays the wound healing. Thus, the promotion of angiogenesis and blood circulation is a linchpin in the process of wound healing. 

Chinese drugs can promote the angiogenesis and metabolism, increase new capillaries and expand the capillaries lumen to form the small arteries and small veins. These regenerated vascular can provide abundant oxygen and essential nutrients for wound healing. It makes the fibroblast proliferation and differentiation and accelerates the granulation tissue rapid growth. 

In rat’s back full-thickness skin defect model, study the effect of Compound Rhubarb Granulation Promoting and Wound Healing Ointment (CRGPWHO was made of Rhubarb, Dracorhodin, Pearl powder and Egg yolk. etc). The capillary permeability of local tissue and the level of wound blood flow in the mid-point were markedly improved. A larger number of new capillaries were found by pathological examination. The results indicated that Chinese medicine can stimulate the neovascularization, improve the blood supply and increase the tissue blood perfusion.

Ninetysix SD rats were randomly divided into 4 groups, with 24 rats in each group, and back wound was made in the rats. For rats in 3 of the 4 groups, hydrocortisone injection was administered to induce chronic wound. Rats in 2 of the 3 groups were treated with WSJPR (a preparation of Chinese drugs) and Xinpukang Granules (XPKG, a preparation of Chinese drugs) respectively, and the rats in the other group were untreated. The rats in the fourth group were taken as control. The wound healing time and the width of new epidermis were observed, and the histomorphological changes and cell cycle of the granulation tissue, and the protein expressions of epidermal growth factor (EGF), transforming growth factorβ1 (TGFβ1) and fibronectin (FN) in the granulation tissue were tested with immunohistochemical technique and flow cytometry.

 The wound healing time of the WSJPR treated and XPKG treated groups was (17.0±1.9) and (18.8±1.9) d respectively, much shorter than that of the untreated and control groups (P<0.05). On the 14th experiment day, the width of new epidermis of the WSJPR treated and XPKG treated groups was (3.73±0.19) and (3.21±0.15) mm respectively, much wider than that of the untreated and control groups (P<0.05). The numbers of angiogenesis, fibroblasts and cells in the S phase in WSJPR treated and XPKG treated groups were much higher than those in the untreated and control groups (P<0.05). Compared with the untreated and control groups, the protein expressions of EGF, TGFβ1 and FN in WSJPR treated and XPKG treated groups were higher (P<0.05).

WSJPR can enhance the wound healing. It was likely through accelerating the cell proliferation and up-regulating the expressions of EGF, TGFβ1 and FN.

 “A total of 90 male sd rats with back full thickness skin lesion were used in this study. Except for the normal control group, the rats were injected with hydrocortisone for inducing chronic skin ulcers, and were randomly divided into untreated group, sijunzi (Chinese drug) decoction group, siwu (Chinese drug) decoction group and bazhen (Chinese drug) decoction group. The time of wound healing was observed; immunohistochemical method and image analytical method were used to test the expressions of vegf and mvc in granulation tissue of dermal chronic ulcers in the rats.”

“Results, in the untreated group, the time of wound healing was significantly longer than that in the normal group (p<0.01). The time of wound healing was obviously shortened in the three treated groups as compared with the untreated group (p<0.01, p<0.05). in the sijunzi decoction group, the time of wound healing was obviously shorter than those in siwu decoction group and bazhen decoction group (p<0.05, p<0.01). In the untreated group, the expression of vegf and mvc were significantly lower than those in the normal control group (p<0.01). The expression of vegf and mvc were obviously increased in the three treated groups as compared with those in the untreated group (p<0.01, p<0.05). In the sijunzi decoction group, the expression of vegf and mvc were obviously lower than those in siwu decoction group and bazhen decoction group (p<0.05, p<0.01).”

“Conclusion: Chinese drugs recipes can promote wound healing in rats through up-regulating the expression of vegf in granulation tissue of dermal chronic ulcers, and inducing angiogenesis.”

2.2. Effect on the number and function of immune cells

 Using chemiluminescence technology found that external use Chinese drugs can activate neutrophils (PMN) and lymphocytes (1y) to generate chemiluminescence. The duration     of luminescence peak is longer. Those activated neutrophils and lymphocytes are in favor of phagocytic bactericidal to prevent wound infection. At the same time, the released immune factors and lymphokine can directly involve in the immune response to provide the necessary conditions for speeding up the wound healing. 

In wound exudate with using Chinese drugs externally, the macrophages is not only more in number, also the intracellular acid phosphatase (ACP) and the glucose metabolic rate-limiting succinate dehydrogenase (SDH) are all maintained at a high level. 

Studies have shown that anti-infective effect of Chinese drugs is by improving the immunity. It is based on the activated Fc and C3b receptors of macrophages membrane surface. Thereby enhancing macrophage function.

In rabbit infected surface wound models found that the number of macrocytes (M) increased during wound healing in Chinese drug group, besides the wandering macrocytes were more than permanent ones. The differences were significant statistically. Through histochemical staining, there was very significant difference of the acid-phosphatase (AcP) and sugar metabolic rate-limiting succinate dehydrogenase (SDH) between Chinese drugs group and control group. It is suggested that external application of Chinese drugs can activate surface wound cells and increase the intracellular enzymic activity to promote the wound healing.

2.3. The level of wound fibronectin (Fn) 

Fibronectin (Fn) play an important role in whole process of wound healing from blood coagulation, debridement, granulation tissue formation and epithelialization, etc. The increase of fibronectin levels is beneficial to wound healing。 

Chinese drugs can significantly increase the Fn content in serum and wounds granulation tissue. Therefore it can accelerate wound healing. 

32 rabbits wound infection model show that external use Chinese drugs can marked increase the Fn in wound, and there is significantly different with the control group (P<0.01).

2.4. Basic fibroblast growth factor (bFGF) 

The bFGF involved in all process of wound healing. It plays initiation, regulation and control role in wound healing. It involved in chemotaxis of inflammatory cells, the fibroblast proliferation, the vascular endothelial cell proliferation and matrix formation. Also have an important impact on the latter maturation Phase.

 In mouse wound model have shown that Chinese drugs can play intelligence role in regulating the level of bFGF. Those are, in the phase of inflammation and proliferation, it can significantly increase the bFGF levels, so as to promote collagen synthesis and wound epithelial growth. However, in the phase of wound remodeling, Chinese drugs can smartly reduce the level of bFGF to promote the degradation of hyperplasia collagen, and make them arranged in an orderly manner to reduce the scar formation.

 In  rats ulcer model, Chinese drugs can increase the level of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in local wound tissue. 

2.5. Collagen synthesis and metabolism

In the wound healing process, typeⅠand Ⅲ collagen play a major role. Type I collagen plays the role of frame, the type Ⅲ collagen wrapps on the frame in the peripheral-type and decided the size of the diameter of collagen fibers and elastic quality. The higher of the type Ⅲ collagen content the finer the collagen fibers, the better the elastic and the lighter the scars.

 In rats full-thickness back skin defects model, by pathology ultrastructure observation shows that the ratio of type Ⅲ and type I collagen is significantly higher in Chinese drugs group’s than that of control group’s in late repair period. It indicates that Chinese drugs can increase the level of type Ⅲ collagen, thereby reducing the scar formation and improve the quality of wounds repairing.

 2.6. Improvement of the nutritional status of the wound

 Amino acid is an important material for granulation tissue growth, the growth quality of granulation tissue related to the level of various amino acids. Lack of amino acids is not conducive to wound healing.

 In  rats full-thickness back skin defects model, in Chinese drugs group’s, the level of glycine, proline, lysine and other 11 kinds of amino acids markedly increasd.

Trace elements Zn closely related to the cell division and protein synthesis, thus affecting wound healing.

In rats plastic ring granuloma model, Chinese drugs marked increase the Zn content in local tissue, play a role in the promotion of wound healing.

2.7. Acidification effect on wound

In alkaline environment, ammonia would form tissue toxin to affect wound healing. In low pH values environment do not produce toxicity. Moreover, the alkalosis make tissue in hypoxic state, it is not conducive to wound healing. The pH value from 7.6 of earlier stage of wound healing reduced to 7.0, the oxyhemoglobin oxygen release increase up to 50%. Because that collagen synthesis and fibroblast growth require oxygen, thus it is conducive to tissue growth by reducing the PH value to enable the oxyhemoglobin releasing more oxygen.

 In animal wounds model, in external use Chinese drugs group’s, the wound pH values reduce from 8 down to about 7.5, while control group’s is 8.14.

2.8. Granulation tissue cells’ proliferation and fibroblasts’ function

The keys for wound healing is the restoration of the cell proliferation. New capillaries and fibroblasts form the granulation tissue cells to fill the wound defect, in favor of reptiles for epithelial cells and promote wound healing.

Modern researches has shown that Chinese drugs can increase the level of wound fibroblasts, promote cell proliferation, trigger the cycle of cell proliferation, accelerate the cell mitotic, enhance the healing activities.

Rat’s chronic refractory wound model, in the Chinese drugs group, the cell number and DNA content was significantly increased in S phase, G2 phase and M phase of new granulation tissue, compared with the control group the difference was significant.

 Animal skin ulcer model, in Chinese drugs group, is not only the number of fibroblasts increased but also the function was active. The cell body enlarged, endoplasmic reticulum highly developed, free ribosomes content was abundant, there were more fine collagen fibers in mesenchyme.

2.9. Promotion of wound contraction materials’ hyperplasia

 Wound contraction has great significance for wound healing: (1) the wound infection chances can be reduced; (2) the wound is smaller, the filling tissue needs fewer.

 The important material for promoting the wound contraction is actins. External use Chinese drugs can promote the secretion of actins in granulation tissue. It is conducive to wound healing.

Animal wound model, in granulation tissue of Chinese drugs group, found a large number of myofibroblasts and its’ synthesis was active, intracellular actins was more, wound contraction was significant than that of control group.

 2.10. Health beneficial wound pus’ secretion

 For chronic refractory wound, external use Chinese drugs can promote the wound secreting a large amount of thick material, it is called pus. This kind of pus is essentially different with the meaning of septic in Western medicine.

 It is nutrient solution secreted from the local micro vessel, rich in immune cells and immune activating factor. It can effectively regulate the function of wound tissue cell. Thus anti-infection and promote wounds healing. In the medium-term of wound healing, the more such pus, the faster wound healing.

2.11. Restoration of original shape and color’s

 Scar is the inevitable outcome of the process of wound healing. In a broad sense, there is no scar there will be no healing. The generation and deposition of scar tissue collagen will increase the strength of healed wound. If the formation of the scar tissue is insufficient, the healed wound tissue can not get enough strength, it will trigger many complications. Such as, the scar may be dehiscence under the internal pressure of human body.

 However, from the aesthetic point of view, the scars have caused the destruction of original appearance. Therefore, in the time of considering the acceleration of wound healing, it is necessary to consider restoring the original shape and color as far as possible. On this point, the Chinese drugs showed a unique advantage.

 By rat’s back skin trauma model，found the mechanism of Chinese drugs on reducing the scar formation. It is through increasing the content of hyaluronic acid (HA) in wound exudates (and maintaining a high level), increasing the ratio of Ⅲ/I collagen and regulate the expression of TGF-β1mRNA.

http://www.ilib2.com/A-ISSN~1006-978X(2001)04-0006-02.html

 SD rats back open wound model, In Chinese drugs group, the epithelial cells growth was fast, healing time was short and the scar size was small, compared with control group had a very significant difference (P<0.01). Electron microscopy observation found that the thickness of collagen fibers was modest, arranged in an orderly manner and showed normal skin morphology.

 2.12. Bacteriostasis

 Total 4 experimental models: 1. Vitro bacteriostasis test in liquid-tube method. 2. Mice subcutaneous abscess made by mixed infection of Candida albicans. 3. Local skin ecchymosis of guinea pig by trauma. 4. Rabbits skin rot caused by subcutaneous

injection of sterile turpentine.

 Results: in vitro, have obvious inhibiting effect for six kinds of common pathogens and opportunistic pathogen that causes mucocutaneous infection. There is also a significant inhibiting effect on infection caused by Candida albicans for mice. Pathological examination showed therapeutic effect on experimental traumatic skin ecchymosis and traumatic skin ulcers by dressing.

2.13.   Promote the recovery of bone fractures

 Bone fracture healing is an extremely complex process of repairing, subject to many factors. How to promote fracture healing early, how to develop drugs to speed up bone healing has been the focus of the orthopedic field. On this field, the Chinese drugs have demonstrated a unique therapeutic effect.

2.13.1. Speed up the reconstruction of blood circulation system

 By direct injecting extract of Chinese drugs on the fracture ends of animals, then checked by test of resistance strength, X-ray and cytology observation. The results showed that the injection can increase the volume of capillary opening up, significantly expanded the capillaries in marrow cavity, improved the permeability of blood vessel walls, and accelerated blood circulation. Thus speed up the fracture healing. 

More than a dozen limbs long bone fracture indolence patients accepted the treatment, length of healing time reduced by an average of 1/3.

2.13.2. Promotion of calcium deposition and enhance the quality of callus

 Rabbit bone fracture model, by callus 45Ca autoradiography determination and micro-morphological observations for the process of fracture healing, in Chinese drugs group, the trabecular osteoid and osteoblasts formed faster, shortened the osteon absorption cycle and in advance into the callus rebuild period.

 Rabbit bone fracture model, after fracture 7, 14, 21, 35, 49 days, determine the callus composition and mechanical properties biologically. Results: in 7, 14, 21 days of Chinese drugs group’s, the content of bone calcium and hydroxyproline was higher than the control group’s. In the 35, 49 days of Chinese drugs group’s, the Charcot-Marie-bending load strength was significantly higher than the control group’s. 

 Rats bone fracture model, after fracture 1 day, 2 weeks, 4 weeks and 6 weeks observed the state of healing. Results: Chinese drugs can significantly reduced the viscosity of plasma and whole blood, improved blood rheology.   So that the blood supply of fracture site has been improved obviously, the hematoma absorption was speeded up. Accelerated fibrous tissue hyperplasia, shortened the process of fibrous callus into osteal callus. Fracture healing was markedly speeded up.

2.13.3. Promotion of growth hormone secretory

Growth hormone (GH) has an important role on bone growth and fracture healing. After fracture the concentration of serum GH increase and at the same time, the pituitary growth hormone cells are in high-functioning state to promote the fracture healing. 

Rabbit model, after gavages Chinese drugs 3, 7, 14 and 28 days, measured the weight of pituitary. By immuno-histochemical staining and image analysis observed the size and gray of pituitary GH cells. Compared with the control group, the weight of pituitary was no different. However, the area and gray of pituitary GH cells of Chinese drugs group’s were markedly increased. The results indicated that Chinese drugs can promote the GH secretion of pituitary GH cells to promote the fracture healing. 

3.13.4. Increase of the level of bone morphogenetic protein

 Bone morphogenetic protein (BMP) can stimulate the development of the cartilage and bone tissue.

A randomized, controlled experiment was conducted. 20 adult dogs were divided two groups: experimented group and controlled group. Three left maxillofacial tooth were pulled out of all dogs, and were implanted with three titanium plats. The dogs of experimental group were ingested with BGC (Chinese drugs capsule). The implanted maxillofacial parts were sampled to observe the changes of implant-bone interface immediately 1, 2, 4, 8, 12 week after the surgery. 

Results: The level of BMP of experimental group is statistically significantly higher than that of controlled group the first week after surgery.

 Conclusion: BGC can promote the osseointegration of oral maxillofacial implants. The mechanism is to induce the release and congregation of BMP.

2.13.5. Promotion of the TGF-β secretion of osteoblast

 TGF–β (Transforming growth factor) is a set of multi-functional peptide that can promote osteoblast proliferation and the fracture healing.

 In vitro cultured calvarial osteoblasts of neonatal SD rats with Chinese drugs, results showed that Chinese drugs can induce the osteoblasts to secrete the TGF-β.

2.13.6.　The generation of IGF-1

 IGF-1 is one of the IGF （insulin-like growth factors）, it can significantly promote the chondrocytes proliferation and synthesis of cartilage matrix, promote the synthesis metabolism of bone and maintain its normal structure and function.

 In vitro cultured calvarial osteoblasts of neonatal SD rats with Chinese drugs, in 14 and 28 days, the serum IGF-1 levels of Chinese drugs group’s was obviously higher than control group's.