Traditional processing, uses, phytochemistry, pharmacology and toxicology of Aconitum sinomontanum Nakai: A comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: As a folk medicine, Aconitum sinomontanum Nakai (Ranunculaceae) a perennial herbaceous flowering plant, is a widely used traditional Chinese medicine. Its rhizomes and roots are known as 'Gaowutou' in China, and it has been traditionally used for the treatment of rheumatoid arthritis, painful swelling of joints, bruises and injuries and has been known to grow well in regions of high altitude such as Gansu, Tibet etc. THE AIM OF THE REVIEW: This systematic review the comprehensive knowledge of the A. sinomontanum, including its traditional processing and uses, chemical constituents, pharmacological activities, toxicity assessment, pharmacokinetics and metabolism, and its use in clinical settings to emphasize the benefits of this species. We also discuss expectations for prospective research and implementation of this herb. This work lays a solid foundation for further development of A. sinomontanum. MATERIALS AND METHOD: Information on the studies of A. sinomontanum was collected from scientific journals, books, and reports via library and electronic data search (PubMed, Elsevier, Scopus, Google Scholar, Springer, Science Direct, Wiley, ACS, EMBASE, Web of Science and CNKI). Meanwhile, it was also obtained from published works of material medica, folk records, ethnopharmacological literatures, Ph.D. and Masters dissertation. RESULTS: As a member of the Ranunculaceae family, A. sinomontanum possesses its up-and-coming biological characteristics. It is widely reported for treating rheumatoid arthritis, painful swelling of joints, bruises and injuries. Currently, over 71 phytochemical ingredients have been obtained and identified from different parts of A. sinomontanum. Among them, alkaloids, flavonoids, steroids, glycosides are the major bioactive constituents. Activities such as antinociceptive, anti-inflammatory, antitumor, antiarrhythmic, local anesthetic, antipyretic, antimicrobial, insecticidal and others have been corroborated in vivo and in vitro. These properties are attributed to different alkaloids. In addition, many of the active ingredients, such as lappaconitine, ranaconitine and total alkaloids have been used as quality markers. CONCLUSION: This work contributes to update the ethnopharmacological uses, chemical constituents, pharmacological activities, toxicity assessment, pharmacokinetics and metabolism, and clinical settings information for A. sinomontanum, which provide basic information to help better understand the pharmacological and toxicological activities of A. sinomontanum in human. However, further in-depth studies are needed to determine the medical uses of this herb and its chemical constituents, pharmacological activities, clinical applications and toxicology.

Selenium Supplementation Alters IL-1ß and IL-6 Protein Levels in Contusion Model Rats.

<b>Background and Objective:</b> Contusion in skeletal muscles were common in athletes.Contusions usually occur when the tissue is exposed to a rapid and strong compressive force, for example, a direct blow, which usually results in the formation of a hematoma within the muscle. Contusion injuries impair the physiological function of the muscle. Supplementation is needed to shorten the healing process. Alternative therapy is antioxidant supplementation. Therefore, we conducted a study on the administration of the antioxidant selenium in contusion rats. <b>Materials and Methods:</b> The subject of this study were male Wistar rats. Rats were divided into 3 groups, namely control group, contusion group and selenium group. Each group consisted of 5 rats. Selenium dose was 0.0513 mg kg¹ b.wt., dissolved into 2% PGA given once a day, for 3 consecutive days. After treatment periods, CK-MM level, IL-1ß and IL-6 level were examined. <b>Results:</b> Protein expression of IL-1ß and IL-6 were significantly lower in the selenium treatment group compared to the contusion group. These results were confirmed by improved step gait in the selenium group. But there was no significant decrease in serum CK-MM levels expression in the selenium treatment group when compared to the contusion group. <b>Conclusion:</b> Selenium supplementation improved gait function after contusion by suppressing IL-1ß and IL-6 expression. However, selenium administration did not alter CK-MM levels.

Gyejibokryeong-Hwan improves recovery of injured muscles in mouse model of muscle contusion.

OBJECTIVE: To investigate the effects of Gyejibokryeong-Hwan (Guizhifuling-wan, GBH) on muscle injury in a mouse model of muscle contusion. METHODS: C57/BL6 mouse biceps femoris muscles were injured using the drop-mass method and injured animals were treated orally with GBH (50, 100, or 500 mg/kg) once a day for 7 d. Open field and treadmill running tests were performed to assess functional recovery from muscle injury. The production of pro-inflammatory cytokines was examined by enzyme-linked immunosorbent assay and Western blotting analysis. Expression of the muscle regeneration biomarkers, myoblast determination (MyoD), myogenic factor 5 (Myf5), and smooth muscle actin (α-SMA), in the biceps femoris muscle was investigated at the protein and mRNA level by Western blotting and real time-PCR, respectively. Histological analysis was performed using hematoxylin and eosin staining. Finally, myosin heavy chain production was investigated in differentiated C2C12 myoblasts in the presence of GBH. RESULTS: GBH treatment markedly improved locomotion and running behavior. GBH significantly inhibited the secretion of monocyte chemoattractant protein-1 into the bloodstream in muscle-contused animals. The levels of MyoD, Myf5, and α-SMA protein and mRNA were significantly up-regulated by GBH in injured muscle tissue. Histological studies suggested that GBH facilitated recovery from muscle damage. However, GBH did not induce the production of myosin heavy chain in vitro. CONCLUSION: Overall, the present study suggested that GBH improves the recovery of the injured muscles in the mouse model of muscle contusion.

Oral non-steroidal anti-inflammatory drugs versus other oral analgesic agents for acute soft tissue injury.

BACKGROUND: Acute soft tissue injuries are common and costly. The best drug treatment for such injuries is not certain, although non-steroidal anti-inflammatory drugs (NSAIDs) are often recommended. There is concern about the use of oral opioids for acute pain leading to dependence. This is an update of a Cochrane Review published in 2015. OBJECTIVES: To assess the benefits or harms of NSAIDs compared with other oral analgesics for treating acute soft tissue injuries. SEARCH METHODS: We searched the CENTRAL, 2020 Issue 1, MEDLINE (from 1946), and Embase (from 1980) to January 2020; other databases were searched to February 2019. SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials involving people with acute soft tissue injury (sprain, strain, or contusion of a joint, ligament, tendon, or muscle occurring within 48 hours of inclusion in the study), and comparing oral NSAIDs versus paracetamol (acetaminophen), opioid, paracetamol plus opioid, or complementary and alternative medicine. The outcomes were pain, swelling, function, adverse effects, and early re-injury. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility, extracted data, and assessed risk of bias. We assessed the quality of the evidence using GRADE methodology. MAIN RESULTS: We included 20 studies, with 3305 participants. Three studies included children only. The others included predominantly young adults; approximately 60% were male. Seven studies recruited people with ankle sprains only. Most studies were at low or unclear risk of bias; however, two were at high risk of selection bias, three were at high risk of bias from lack of blinding, and five were at high risk of selective outcome reporting bias. Some evidence relating to pain relief was high certainty. Other evidence was either moderate, low or very low certainty, reflecting study limitations, indirectness, imprecision, or combinations of these. Thus, we are certain or moderately certain about some of the estimates, and uncertain or very uncertain of others. Eleven studies, involving 1853 participants compared NSAIDs with paracetamol. There were no differences between the two groups in pain at one to two hours (1178 participants, 6 studies; high-certainty evidence), at days one to three (1232 participants, 6 studies; high-certainty evidence), and at day seven or later (467 participants, 4 studies; low-certainty evidence). There was little difference between the groups in numbers of participants with minimal swelling at day seven or later (77 participants, 1 study; low-certainty evidence). Very low-certainty evidence from three studies (386 participants) means we are uncertain of the finding of little difference between the two groups in return to function at day seven or later. There was low-certainty evidence from 10 studies (1504 participants) that NSAIDs may slightly increase the risk of gastrointestinal adverse events compared with paracetamol. There was low-certainty evidence from nine studies (1679 participants) of little difference in neurological adverse events between the NSAID and paracetamol groups. Six studies, involving 1212 participants compared NSAIDs with opioids. There was moderate-certainty evidence of no difference between the groups in pain at one hour (1058 participants, 4 studies), and low-certainty evidence for no difference in pain at days four or seven (706 participants, 1 study). There was very low-certainty evidence of no important difference between the groups in swelling (84 participants, 1 study). Participants in the NSAIDs group were more likely to return to function in 7 to 10 days (542 participants, 2 studies; low-certainty evidence). There was moderate-certainty evidence (1143 participants, 5 studies) that NSAIDs were less likely to result in gastrointestinal or neurological adverse events compared with opioids. Four studies, involving 240 participants, compared NSAIDs with the combination of paracetamol and an opioid. The applicability of findings from these studies is in question because the dextropropoxyphene combination analgesic agents used are no longer in general use. Very low-certainty evidence means we are uncertain of the findings of no differences between the two interventions in the numbers with little or no pain at day one (51 participants, 1 study), day three (149 participants, 2 studies), or day seven (138 participants, 2 studies); swelling (230 participants, 3 studies); return to function at day seven (89 participants, 1 study); and the risk of gastrointestinal or neurological adverse events (141 participants, 3 studies). No studies reported re-injury rates. No studies compared NSAIDs with oral complementary and alternative medicines, AUTHORS' CONCLUSIONS: Compared with paracetamol, NSAIDs make no difference to pain at one to two hours and at two to three days, and may make no difference at day seven or beyond. NSAIDs may result in a small increase in gastrointestinal adverse events and may make no difference in neurological adverse events compared with paracetamol. Compared with opioids, NSAIDs probably make no difference to pain at one hour, and may make no difference at days four or seven. NSAIDs probably result in fewer gastrointestinal and neurological adverse effects compared with opioids. The very low-certainly evidence for all outcomes for the NSAIDs versus paracetamol with opioid combination analgesics means we are uncertain of the findings of no differences in pain or adverse effects. The current evidence should not be extrapolated to adults older than 65 years, as this group was not well represented in the studies.

Protective Effects of Resveratrol Supplementation on Contusion Induced Muscle Injury.

Muscle injuries frequently occur in contact sports events. The current treatment options for soft tissue injuries remain suboptimal and often result in delayed or incomplete recovery of damaged muscles. Resveratrol (RES) is a phenolic phytochemical, well-known for its antioxidant and anti-inflammatory properties. The purpose of this study is to evaluate the potential beneficial effects of RES supplementation on inflammation and regeneration in skeletal muscle after a contusion injury, in comparison to a conventional treatment of nonsteroidal anti-inflammatory drugs (NSAID). After one week of acclimation, forty eight -week-old male ICR mice were randomly divided into the five groups (n=8 per group): 1) normal control (NC), 2) mass-drop injury without any treatment (mass-drop injury, MDI), 3) post-injury NSAID treatment (MDI+ 10mg/kg NSAID), 4) post-injury RES supplementation (MDI+ 25mg/kg/day RES) and 5) post-injury treatment with RES and NSAID (MDI + resveratrol+ NSAID). After muscle contusion injury of the left gastrocnemius muscle, RES or NSAID were orally administered post-injury once a day for 7 days. Results showed that the MDI group had significantly higher serum uric acid (UA), CREA (creatinine), LDH (lactic dehydrogenase) and creatine kinase (CK) than the normal control group. Treatment with resveratrol reduced muscle damage as evidenced by the significantly decreased serum levels of UA, CREA, LDH and CK after contusion-induced muscle injuries in mice. In addition, RES and RES + NSAID groups promoted muscle satellite cell regeneration with increase in desmin protein after injury. Our results suggest that resveratrol combined with NSAID potentially improve muscle recovery and may be a potential candidate for further development as an effective clinical treatment for muscle repair.

Anti-inflammatory and antioxidant effect of melatonin on recovery from muscular trauma induced in rats.

In recent decades, the number of people who practice sports has grown exponentially, increasing the number of muscular injuries. Trauma injury occurs when the muscle is exposed to a sudden compression force. Melatonin (MLT) has often been cited in the literature as a potent antioxidant and anti-inflammatory agent. This study was designed to evaluate MLT action on muscle tissue in Wistar rats in an experimental model of muscle trauma. Twenty-eight Wistar rats were used, divided into four groups: CO (Control), CO + MLT (Control + Melatonin), T (Trauma) and T + MLT (Trauma + Melatonin). MLT (20 mg/kg) was administered (ip) daily at dusk until day 7. The trauma occurred on day 1, 2 h before the first MLT application. On day 8, muscle tissue was collected for histological analysis (HE), immunohistochemistry (TNF-α and NFκB), evaluation of oxidative stress through analysis of lipoperoxidation by TBARS and activity of SOD and GPx enzymes, and analysis of nitrites and nitrates. In the evaluation of TBARS and SOD, we observed a significant increase in the T group and a significant decrease in the T + MLT group. In the evaluation of GPx, there was a significant increase in the T group and a significant decrease in the T + MLT group. The histological analysis of muscle tissue revealed structural changes of muscle fibers and inflammatory infiltrate in the T group but a decrease in this damage in the T + MLT group. In the immunohistochemical evaluation, increased expression of TNFα and NFκB proteins in the T group was observed and a significant decrease of this expression in the T + MLT group. MLT was shown to attenuate oxidative damage and to diminish the expression of inflammatory proteins and tissue damage in this experimental model.

Effects of photobiomodulation therapy and topical non-steroidal anti-inflammatory drug on skeletal muscle injury induced by contusion in rats-part 2: biochemical aspects.

Muscle injuries trigger an inflammatory process, releasing important biochemical markers for tissue regeneration. The use of non-steroidal anti-inflammatory drugs (NSAIDs) is the treatment of choice to promote pain relief due to muscle injury. NSAIDs exhibit several adverse effects and their efficacy is questionable. Photobiomodulation therapy (PBMT) has been demonstrated to effectively modulate inflammation induced from musculoskeletal disorders and may be used as an alternative to NSAIDs. Here, we assessed and compared the effects of different doses of PBMT and topical NSAIDs on biochemical parameters during an acute inflammatory process triggered by a controlled model of contusion-induced musculoskeletal injury in rats. Muscle injury was induced by trauma to the anterior tibial muscle of rats. After 1 h, rats were treated with PBMT (830 nm, continuous mode, 100 mW of power, 35.71 W/cm2; 1, 3, and 9 J; 10, 30, and 90 s) or diclofenac sodium (1 g). Our results demonstrated that PBMT, 1 J (35.7 J/cm2), 3 J (107.1 J/cm2), and 9 J (321.4 J/cm2) reduced the expression of tumor necrosis factor alpha (TNF-α) and cyclooxygenase-2 (COX-2) genes at all assessed times as compared to the injury and diclofenac groups (p < 0.05). The diclofenac group showed reduced levels of COX-2 only in relation to the injury group (p < 0.05). COX-2 protein expression remained unchanged with all therapies except with PBMT at a 3-J dose at 12 h (p < 0.05 compared to the injury group). In addition, PBMT (1, 3, and 9 J) effectively reduced levels of cytokines TNF-α, interleukin (IL)-1ß, and IL-6 at all assessed times as compared to the injury and diclofenac groups (p < 0.05). Thus, PBMT at a 3-J dose was more effective than other doses of PBMT and topical NSAIDs in the modulation of the inflammatory process caused by muscle contusion injuries.

Melatonin: is it an effective antioxidant for pulmonary contusion?

BACKGROUND: The goal of the present study was to evaluate the antioxidant effects of melatonin on pulmonary contusion (PC) caused by isolated blunt thoracic trauma (BTT) in an experimental rat model. MATERIALS AND METHODS: A total of 49 rats were divided into three groups: control group (CG), trauma group (TG), and melatonin group (MG). PC was induced by isolated BTT for all the groups except the control group. Intraperitoneal melatonin was administered to the MG after trauma. Blood and tissue samples were collected from the groups. Malondialdehyde (MDA), total oxidant capacity and total antioxidant capacity (TAOC), arterial blood gas, and other biochemical parameters such as urea, creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase were measured. Lung tissue samples were collected for histopathology. RESULTS: On day 2, blood MDA and total oxidant capacity levels were lower, and TAOC levels were higher in the MG compared with the TG (P < 0.001). Blood pH, PO2, and PCO2 of the MG significantly improved on day 2 compared with the TG (P ≤ 0.001). Compared with the TG, histologic damage scores of the MG decreased on day 2 (P = 0.013). Urea, creatinine, ALT, and aspartate aminotransferase levels of the MG on day 2 were lower than TG parameters (P = 0.01, P = 0.02, P = 0.05, and P < 0.001, respectively). CONCLUSIONS: Our findings demonstrate that melatonin can improve the histopathology of PC and distant organs such as liver and kidney by diminishing oxidative stress. All these findings suggest that melatonin may be an effective new therapeutic agent for PC caused by BTT.

The Effects of Dexamethasone and L-NAME on Acute Lung Injury in Rats with Lung Contusion.

The therapeutic efficiency of an anti-inflammatory agent, dexamethasone (DXM), and a nitric oxide synthase (NOS) inhibitor, Nitro-L-arginine methyl ester (L-NAME), in lung tissue injury after lung contusion was investigated. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), YKL-40, an inflammatory peptide, inducible NOS (iNOS), and Clara cell protein 16 (CC-16) were evaluated. Immunohistochemical analyses were also performed, and the lung tissue was examined histopathologically. The study consisted of eight groups of Sprague-Dawley rats (n = 10 in each group), weighing 250-300 g: (1) control, (2) contusion, (3) control + DXM, (4) contusion + DXM, (5) control + L-NAME (6) contusion + L-NAME, (7) control + DXM + L-NAME, and (8) contusion + DXM + L-NAME. A previously developed lung contusion model was used, in addition to the control group. The rats were administered DXM and L-NAME intraperitoneally (i.p.) at doses of 15 and 60 mg/kg/day, respectively. DXM and L-NAME administration decreased the iNOS level in the contusion groups. DXM increased the levels of YKL-40 and IL-10 in both the control and contusion groups, with higher levels in the contusion groups. L-NAME increased the serum level of IL-10 in the lung contusion groups. DXM increased the synthesis of CC-16 in the control and contusion groups. The combined use of a high-dose steroid and NOS inhibitor resulted in the death of the rats. Steroids can increase the level of cytokines, such as YKL-40 and IL-10, and the synthesis of CC-16 and prevent pneumonia, ALI/ARDS, and sepsis in lung contusion.

Oral non-steroidal anti-inflammatory drugs versus other oral analgesic agents for acute soft tissue injury.

BACKGROUND: Acute soft tissue injuries are common and costly. The best drug treatment for such injuries is not certain, although non-steroidal anti-inflammatory drugs (NSAIDs) are often recommended. OBJECTIVES: To assess the effects (benefits and harms) of NSAIDs compared with other oral analgesics for treating acute soft tissue injuries. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (12 September 2014), the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2014 Issue 8), MEDLINE (1966 to September 2014), EMBASE (1980 to September 2014), CINAHL (1937 to November 2012), AMED (1985 to November 2012), International Pharmaceutical Abstracts (1970 to November 2012), PEDro (1929 to November 2012), and SPORTDiscus (1985 to November 2012), plus internet search engines, trial registries and other databases. We also searched reference lists of relevant articles and contacted authors of retrieved studies and pharmaceutical companies to obtain relevant unpublished data. SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials involving people with acute soft tissue injury (sprain, strain or contusion of a joint, ligament, tendon or muscle occurring up to 48 hours prior to inclusion in the study) and comparing oral NSAID versus paracetamol (acetaminophen), opioid, paracetamol plus opioid, or complementary and alternative medicine. The outcomes were pain, swelling, function, adverse effects and early re-injury. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed studies for eligibility, extracted data and assessed risk of bias. We assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. MAIN RESULTS: We included 16 trials, with a total of 2144 participants. Two studies included children only. The other 14 studies included predominantly young adults, of whom over 60% were male. Seven studies recruited people with ankle sprains only. Most studies were at low or unclear risk of bias; however, two were at high risk of selection bias, three were at high risk of bias from lack of blinding, one was at high risk of bias due to incomplete outcome data, and four were at high risk of selective outcome reporting bias. The evidence was usually either low quality or very low quality, reflecting study limitations, indirectness such from as suboptimal dosing of single comparators, imprecision, or one or more of these. Thus we are either uncertain or very uncertain of the estimates.Nine studies, involving 991 participants, compared NSAIDs with paracetamol. While tending to favour paracetamol, there was a lack of clinically important differences between the two groups in pain at less than 24 hours (377 participants, 4 studies; moderate-quality evidence), at days 1 to 3 (431 participants, 4 studies; low quality), and at day 7 or over (467 participants, 4 studies; low quality). A similar lack of difference between the two groups applied to swelling at day 3 (86 participants, 1 study; very low quality) and at day 7 or over (77 participants, 1 study; low quality). There was little difference between the two groups in return to function at day 7 or over (316 participants, 3 studies; very low quality): based on an assumed recovery of function of 804 per 1000 participants in the paracetamol group, 8 fewer per 1000 recovered in the NSAID group (95% confidence interval (CI) 80 fewer to 73 more). There was low-quality evidence of a lower risk of gastrointestinal adverse events in the paracetamol group: based on an assumed risk of gastrointestinal adverse events of 16 per 1000 participants in the paracetamol group, 13 more participants per 1000 had a gastrointestinal adverse event in the NSAID group (95% CI 0 to 35 more).Four studies, involving 958 participants, compared NSAIDs with opioids. Since a study of a selective COX-2 inhibitor NSAID (valdecoxib) that was subsequently withdrawn from the market dominates the evidence for this comparison (706 participants included in the analyses for pain, function and gastrointestinal adverse events), the applicability of these results is in doubt and we give only a brief summary. There was low quality evidence for a lack of clinically important differences between the two groups regarding pain at less than 24 hours, at days 4 to 6, and at day 7. Evidence from single studies showed a similar lack of difference between the two groups for swelling at day 3 (68 participants) and day 10 (84 participants). Return to function at day 7 or over favoured the NSAID group (low-quality), and there were fewer gastrointestinal adverse events in the selective COX-2 inhibitor NSAID group (very low quality).Four studies, involving 240 participants, compared NSAIDs with the combination of paracetamol and an opioid. The applicability of findings from these studies is partly in question because the dextropropoxyphene combination analgesic agents used are no longer in general use. While the point estimates favoured NSAID, the very low-quality evidence did not show a difference between the two interventions in the numbers with little or no pain at day 1 (51 participants, 1 study), day 3 (149 participants, 2 studies), or day 7 (138 participants, 2 studies). Very low-quality evidence showed a similar lack of difference between the two groups applied to swelling at day 3 (reported in two studies) and at day 7 (reported in two studies), in return to function at day 7 (89 participants, 1 study), and in gastrointestinal adverse events (141 participants, 3 studies).No studies compared NSAIDs with complementary and alternative medicines, and no study reported re-injury rates. AUTHORS' CONCLUSIONS: There is generally low- or very low-quality but consistent evidence of no clinically important difference in analgesic efficacy between NSAIDs and other oral analgesics. There is low-quality evidence of more gastrointestinal adverse effects with non-selective NSAID compared with paracetamol. There is low- or very low-quality evidence of better function and fewer adverse events with NSAIDs compared with opioid-containing analgesics; however, one study dominated this evidence using a now unavailable COX-2 selective NSAID and is of uncertain applicability. Further research is required to determine whether there is any difference in return to function or adverse effects between both non-selective and COX-2 selective NSAIDs versus paracetamol.

Effects of electroacupuncture on recovery of the electrophysiological properties of the rabbit gastrocnemius after contusion: an in vivo animal study.

BACKGROUND: Our preliminary studies indicated that electroacupuncture (EA) at the ST36 and Ashi acupoints could promote regeneration of the rabbit gastrocnemius (GM) by improving microcirculation perfusion, promoting the recovery of myofiber structures, and inhibiting excessive fibrosis. However, the effects of EA on recovery of the electrophysiological properties of the GM after contusion are not yet clear. Thus, the purpose of this study was to investigate the effects of EA at the Zusanli (ST36) and Ashi acupoints with regard to recovery of the electrophysiological properties of the rabbit GM after contusion. METHODS: Forty-five rabbits were randomly divided into three groups: normal, contusion, and EA. After an acute GM contusion was produced (in rabbits in the contusion and EA groups), rabbits in the EA group were treated with electrostimulation at the ST36 and Ashi acupoints with 0.4 mA (2 Hz) for 15 min. The contusion group received no EA treatment. At different time points (7, 14, and 28 days) after contusion, we performed surface electromyography (EMG) and measured the nerve conduction velocity (NCV) of the GM and the GM branch of the tibial nerve. We also examined acetylcholinesterase (AchE) and Agrin expression in the neuromuscular junction (NMJ) via immunohistochemistry. RESULTS: Compared with the contusion group, the EMG amplitude and NCV in rabbits in the EA group were significantly higher at all time points after contusion. AchE and Agrin expression in the EA group were significantly higher than those in the contusion group. CONCLUSIONS: Our results showed that EA at the ST36 and Ashi acupoints effectively promoted recovery of the electrophysiological properties of the rabbit GM after contusion. The effects of EA were realized by promotion of the regeneration of myofibers and nerve fibers, as well as acceleration of NMJ reconstruction by upregulation of AchE and Agrin expression in the motor endplate area.

Chronic Prosopis glandulosa treatment blunts neutrophil infiltration and enhances muscle repair after contusion injury.

The current treatment options for soft tissue injuries remain suboptimal and often result in delayed/incomplete recovery of damaged muscle. The current study aimed to evaluate the effects of oral Prosopis glandulosa treatment on inflammation and regeneration in skeletal muscle after contusion injury, in comparison to a conventional treatment. The gastrocnemius muscle of rats was subjected to mass-drop injury and muscle samples collected after 1-, 3 h, 1- and 7 days post-injury. Rats were treated with P. glandulosa (100 mg/kg/day) either for 8 weeks prior to injury (up until day 7 post-injury), only post-injury, or with topically applied diclofenac post-injury (0.57 mg/kg). Neutrophil (His48-positive) and macrophage (F4/80-positive) infiltration was assessed by means of immunohistochemistry. Indicators of muscle satellite cell proliferation (ADAM12) and regeneration (desmin) were used to evaluate muscle repair. Chronic P. glandulosa and diclofenac treatment (p<0.0001) was associated with suppression of the neutrophil response to contusion injury, however only chronic P. glandulosa treatment facilitated more effective muscle recovery (increased ADAM12 (p<0.05) and desmin (p<0.001) expression), while diclofenac treatment had inhibitory effects on repair, despite effective inhibition of neutrophil response. Data indicates that P. glandulosa treatment results in more effective muscle repair after contusion.

[Comparative Study on Effects of Anti-contusion Injury, Analgesia and Anti-inflammation of Root and Stem of Zanthoxylum nitidum].

OBJECTIVE: To provide the scientific evidence for expansion of medicinal parts of Zanthoxylum nitidum by comparing the effects of anti-contusion injury, analgesia and anti-inflammation of its root and stem. METHODS: The pharmacological effects between root and stem of Zanthoxylum nitidum were compared by observing the anti-injury effect in rats with injury struck by hammer. The analgesic effect in mice was evaluated by writhing test and hot plate test, and the anti-inflammatory effect on paw edema induced by carrageenan and granuloma induced by cotton pellet were investigated in rats. RESULTS: Both root and stem of Zanthoxylum nitidum relieved the exterior and histological symptoms of rats' injury legs struck by hammer, decreased the numbers of mice's writhing, enhanced pain threshold of mice on heat plate, inhibited the edema of rats induced by carrageenan, and suppressed the granuloma of rats induced by cotton pellet. CONCLUSION: Stem of Zanthoxylum nitidum has similar effects of anti-contusion injury, analgesia and anti-inflammation with root of Zanthoxylum nitidum.

Does urinary trypsin inhibitor have a role in acute lung injury induced by pulmonary contusion: a basic research in a model of rats.

We evaluate the efficacy of urinary trypsin inhibitor (UTI) on inflammation, oxidative stress, hypoxemia, and diseased lesion in a rat model of acute lung injury induced by blunt trauma. Rats were allocated to 4 groups. One group served as normal control. The other 3 groups had a moderate pulmonary contusion. Except for 1 sham group administrated saline, 1 group was administrated low-dose UTI (20,000 U/kg), and another group was administrated high-dose UTI (50,000 U/kg). Twelve hours after contusion, neutrophil counting in bronchoalveolar lavage fluid (BALF) was performed and tumor necrosis factor α level and albumin level in BALF was tested. Lung tissue malondialdehyde levels, superoxide dismutase, and catalase activity was investigated, and blood gas analysis and contusion volume quantification using 3-dimensional computed tomography were performed. High-dose UTI significantly decreased neutrophil count and tumor necrosis factor α level in BALF (P<0.05) and decreased albumin level in BALF but without significance. Lung tissue malondialdehyde levels was significantly reduced, whereas superoxide dismutase and catalase activity were elevated by UTI with significance (P<0.05) especially high-dose UTI. No statistical significance was seen in the change in arterial oxygen partial pressure (PaO2) and contusion volume by UTI (P>0.05). UTI has a dose-dependent trend to ameliorate inflammatory and oxygen stress in pulmonary contusion-induced acute lung injury. However, the effect on hypoxemia and contusion lesion and the best administration regime should be investigated in future study.

The protective role of MnTBAP in oxidant-mediated injury and inflammation in a rat model of lung contusion.

BACKGROUND: Lung contusion (LC) is a unique direct and focal insult that is considered a major risk factor for the initiation of acute lung injury and acute respiratory distress syndrome. We have shown recently that consumption of nitric oxide (due to excess superoxide) resulting in peroxynitrite formation leads to decreased vascular reactivity after LC. In this study, we set out to determine whether the superoxide scavenger Mn (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) plays a protective role in alleviating acute inflammatory response and injury in LC. METHODS: Nonlethal, closed-chest, bilateral LC was induced in a rodent model. Administration of the superoxide dismutase mimetic MnTBAP concurrently in LC in rats was performed, and bronchoalveolar lavage (BAL) and lung samples were analyzed for degree of injury and inflammation at 5 and 24 h after the insult. The extent of injury was assessed by the measurement of cells and albumin with cytokine levels in the BAL and lungs. Lung samples were subjected to H&E and superoxide staining with dihydro-ethidium. Protein-bound dityrosine and nitrotyrosine levels were quantified in lung tissue by tandem mass spectrometry. RESULTS: The degrees of lung injury after LC as determined by BAL albumin levels were significantly decreased in the MnTBAP-administered rats at all the time points when compared to the corresponding controls. The release of proinflammatory cytokines and BAL neutrophils was significantly less in the rats administered MnTBAP after LC. Administration of MnTBAP decreased tissue damage and decreased necrosis and neutrophil-rich exudate at the 24-h time point. Staining for superoxide anions showed significantly greater intensity in the lung samples from the LC group compared to the LC+ MnTBAP group. High-performance liquid chromatography/tandem mass spectrometry revealed that MnTBAP treatment significantly attenuated dityrosine and nitrotyrosine levels, consistent with decreased oxidant injury. CONCLUSION: Superoxide dismutase mimetic-MnTBAP reduced permeability and oxidative injury in LC and may have a therapeutic role in diminishing inflammation in LC.

Soft tissue contusion repairing effects of Hong Yao with different penetration enhancers.

ETHNOPHARMACOLOGICAL RELEVANCE: Hong Yao aerosol (HYA) is a new dosage form developed from Hong Yao, a traditional Chinese medicine preparation, which has the efficacy of promoting soft tissue contusion repair, anti-inflammation, and analgesia. AIM: To evaluate the soft tissue contusion repairing, anti-inflammatory and analgesic effects of HYA formulations with different penetration enhancers (PE) and to quantify the transdermal absorption of HYA component. MATERIALS AND METHODS: Three preparations of HYA with different PEs were made: DMSO preparation (5% DMSO as additional PE), Azone preparation (3% azone as additional PE), and NAPE preparation (no additional PE). Four in vivo rodent models were employed to evaluate the pharmacodynamic effects of the HYAs: mouse soft tissue contusion model, rat paw edema model, mouse ear swelling model, and mouse analgesia model of electric-stimulated foot. In vitro skin penetration experiment was applied to evaluate the transdermal absorption of HYA components. RESULTS: All HYA preparations showed effects on soft tissue contusion repairing, anti-inflammation, and analgesia compared with the blank control (p<0.05). There was no significant difference among the three preparations. Pathological variation of mice skin and the pain response time (PRT) reduction phenomena indicated that DMSO preparation induced skin irritation. In vitro skin penetration experiment showed no significant difference between DMSO and NAPE on absorption enhancement of ferulic acid from HYA. CONCLUSIONS: NAPE preparation was considered as best and Menthol/borneol (6.3%, W/W, 4:1.75) in HYA might be a good PE combination.

Curative effect of Xuebijing injection on severe pulmonary contusion.

OBJECTIVE: To investigate the curative effects of Xuebijing (XBJ) injection, a Chinese patent medicine, on severe pulmonary contusion (PC). METHODS: Sixty-three patients with PC were randomized to conventional therapy plus XBJ injection (n = 33) or conventional therapy alone (n = 30). Between groups differences in corticosteroid treatment, immune regulation therapy, hemofiltration, infusion volume, transfusion volume and antibiotic period were measured, as were intensive care unit (ICU)-free time, ventilation time, 28-day mortality rate and incidence of ventilation-associated pneumonia (VAP). Serum concentrations of procalcitonin (PCT), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-10, white blood cell (WBC) counts and percentages of human leukocyte antigen DR/ CD14+ (HLA-DR/CD14+) peripheral blood mononuclear cells were compared. Markers of ventilation were determined by blood gas analysis and ventilator parameters. RESULTS: WBC counts and serum concentrations of PCT, TNF-alpha, IL-6 and IL-10 were reduced significantly more quickly, and CD14+ percentage was increased significantly earlier, in the XBJ group than in the control group (P < 0.05 each).The level of ventilation and oxygenation index were ameliorated earlier in the XBJ than in the control group (P < 0.05). XBJ treatment significantly reduced ICU-free time, ventilation time and incidence of VAP (P < 0.05 each), but had no effect on 28-day mortality rate CONCLUSION: XBJ treatment can shorten ICU-free and ventilation times and reduce the incidence of VAP, improving outcomes in patients with severe PC. XBJ may act by regulating inflammation and immunity, alleviating systemic inflammatory response syndrome induced by trauma.

Postcontusion polyphenol treatment alters inflammation and muscle regeneration.

PURPOSE: Given the major role that oxidants play in cellular damage, and the recent focus on antioxidants as treatment for muscle injuries, the aim of this study was to examine the effect of short-term postinjury grape seed-derived polyphenol supplementation on muscle inflammation and repair processes after contusion injury. METHODS: Experimental injury of the right gastrocnemius muscle was achieved by drop-mass method (200 g from a height of 50 cm), after which rats were gavaged with either 0.9% saline (placebo-PLA) or 20 mg·kg⁻¹·d⁻¹ of proanthocyanidolic oligomer (PCO) from 2 h after contusion injury, for up to 14 d after injury. Blood samples and injured muscle were collected at 4 h and at days 1, 3, 5, 7, and 14 after injury. RESULTS: Compared to an uninjured control group, PCO supplementation resulted in an earlier peak in number of activated satellite cells in contusion-injured muscle tissue (4 h for PCO vs day 3 for PLA, n = 4 per time point per group) and fetal myosin heavy chain expression (day 5 for PCO, P < 0.01 with no change in PLA, n = 3 per time point per group), indicative of quicker muscle regeneration. PCO supplementation limited neutrophil infiltration and facilitated earlier macrophage infiltration into the injured area (n = 4 per group). PCO also resulted in an earlier return toward control levels of muscle proinflammatory cytokines on day 3 (P < 0.01 for interleukin 6 and P < 0 05 for tumor necrosis factor α, both n = 3 per group). CONCLUSIONS: Data show that short-term postinjury PCO supplementation was able to quicken muscle regeneration by facilitating earlier recruitment of activated satellite cells and to modulate the immune system in favor of an anti-inflammatory status.

Accelerated resolution of laser-induced bruising with topical 20% arnica: a rater-blinded randomized controlled trial.

BACKGROUND: Dermatological procedures can result in disfiguring bruises that resolve slowly. OBJECTIVES: To assess the comparative utility of topical formulations in hastening the resolution of skin bruising. METHODS: Healthy volunteers, age range 21-65 years, were enrolled for this double (patient and rater) blinded randomized controlled trial. For each subject, four standard bruises of 7 mm diameter each were created on the bilateral upper inner arms, 5 cm apart, two per arm, using a 595-nm pulsed-dye laser (Vbeam; Candela Corp., Wayland, MA, U.S.A.). Randomization was used to assign one topical agent (5% vitamin K, 1% vitamin K and 0·3% retinol, 20% arnica, or white petrolatum) to exactly one bruise per subject, which was then treated under occlusion twice a day for 2 weeks. A dermatologist not involved with subject assignment rated bruises [visual analogue scale, 0 (least)-10 (most)] in standardized photographs immediately after bruise creation and at week 2. RESULTS: There was significant difference in the change in the rater bruising score associated with the four treatments (anova, P=0·016). Pairwise comparisons indicated that the mean improvement associated with 20% arnica was greater than with white petrolatum (P=0·003), and the improvement with arnica was greater than with the mixture of 1% vitamin K and 0·3% retinol (P=0·01). Improvement with arnica was not greater than with 5% vitamin K cream, however. CONCLUSIONS: Topical 20% arnica ointment may be able to reduce bruising more effectively than placebo and more effectively than low-concentration vitamin K formulations, such as 1% vitamin K with 0·3% retinol.