Real-world practice in Peyronie's disease management: Results from a national survey of urologists.

BACKGROUND: Despite many available treatments for Peyronie's disease (PD), practice patterns of available therapeutics are not well characterized. OBJECTIVE: We conducted a national survey of urologists to characterize real-world practice patterns of PD management and to characterize the use of therapies discouraged by the American Urological Association guidelines on PD management. MATERIALS AND METHODS: A 34-item survey was distributed via RedCap to urologists who treat patients with PD in all American Urological Association sections. Questions elicited demographic information as well as practices in the diagnosis and treatment of PD. Comparisons were made with Pearson's chi-squared test. The primary outcome was reported use of therapies discouraged by the American Urological Association guidelines on PD. RESULTS: A total of 145 respondents completed the survey, of whom 19% were fellowship trained in andrology/sexual medicine, 36% practiced in an academic setting, and 50% had at least 20 years in practice. Only 60% of respondents reporting performing in-office curvature assessment prior to commencing intralesional injection or surgical treatment, with higher prevalence in andrology/sexual medicine fellowship-trained versus non-fellowship-trained urologists (85% vs. 54%, p = 0.003). The most popular treatment modalities were collagenase clostridium histolyticum (61% of respondents), phosphodiesterase-5 inhibitors (54%), and penile traction (53%). Twenty-one percent of respondents reported currently using a treatment that is explicitly discouraged by the American Urological Association guidelines (extracorporeal shockwave therapy for curvature, L-carnitine, omega-3 fatty acids, or vitamin E). DISCUSSION: Patients seeking PD treatment may be offered different therapies, some of which are not evidence-based, depending on the treating urologist. This study is limited by self-selection and response bias. Its strength is that it represents a cross-sectional overview of real-world practice patterns in PD management, which has not been previously described. CONCLUSIONS: A significant proportion of urologists reported PD management practices that are not evidence-based and not guideline-supported.

A systematic review of non-surgical management in Peyronie's disease.

The efficacy of many non-surgical treatments for Peyronie's disease is unclear. This systematic review aims to critically assess the currently available options and provide a recommendation for treatment based on this. A systematic literature search utilising the Medline (Pubmed), Embase, global health and Cochrane library databases was conducted up to May 2021. All randomised controlled trials assessing non-surgical treatment modalities for Peyronie's Disease were included. Individual study risk of bias was evaluated using the Cochrane tool and GRADE was used to assess evidence strength. Outcome measures were the change in penile curvature (degrees), plaque size (volume or size), International Index of Erectile Function score, pain scores and change in penile length. Prospero registration number: CRD42017064618. Amongst the 5549 articles identified, 41 studies (42 reports) were included. Seven different oral treatment options including vitamin E supplementation showed evidence for improving outcomes such as penile curvature and plaque size. Of the intralesional treatments, Collagenase Clostridium Histolyticum showed evidence for improving penile curvature (Range: 16.3-17 degrees, moderate level certainty of evidence). Intralesional Interferon demonstrated some improvement in curvature (Range: 12-13.5 degrees), plaque size (Range: 1.67-2.2 cm2) and pain, whilst intralesional calcium channel blockers such as Verapamil showed variable evidence for changes in the plaque size and pain. Extracorporeal Shockwave Therapy consistently demonstrated evidence for improving penile pain in stable disease, and two mechanical traction devices improved curvature. Iontophoresis, topical medications, and combination therapies did not demonstrate any consistent improvements in outcome measures. Intralesional options demonstrate the best potential. Overall, results varied with few high-quality randomised trials present.

Extracellular matrix and Hippo signaling as therapeutic targets of antifibrotic compounds for uterine fibroids.

BACKGROUND: Uterine fibroids are highly prevalent, collagen-rich, mechanically stiff, fibrotic tumors for which new therapeutic options are needed. Increased extracellular matrix (ECM) stiffness activates mechanical signaling and Hippo/YAP promoting fibroid growth, but no prior studies have tested either as a therapeutic target. We tested the hypothesis that injection of a purified form of collagenase Clostridium histolyticum (CCH) that selectively digests type I and type III collagens would alter ECM stiffness, Hippo signaling, and selectively reduce fibroid cell growth. We also used two FDA-approved drugs, verteporfin and nintedanib, to elucidate the role of Hippo/YAP signaling in uterine fibroid and myometrial cells. METHODS: The clinical trial was registered (NCT02889848). Stiffness of samples was measured by rheometry. Protein expression in surgical samples was analyzed via immunofluorescence. Protein and gene expression in uterine fibroid or myometrial cell lines were measured by real time PCR and western blot, and immunofluorescence. RESULTS: Injection of CCH at high doses (0.1-0.2 mg/cm3 ) into fibroids resulted in a 46% reduction in stiffness in injected fibroids compared to controls after 60 days. Levels of the cell proliferation marker proliferative cell nuclear antigen (PCNA) were decreased in fibroids 60 days after injection at high doses of CCH. Key Hippo signaling factors, specifically the transcriptionally inactive phosphorylated YAP (p-YAP), was increased at high CCH doses, supporting the role of YAP in fibroid growth. Furthermore, inhibition of YAP via verteporfin (YAP inhibitor) decreased cell proliferation, gene and protein expression of key factors promoting fibrosis and mechanotransduction in fibroid cells. Additionally, the anti-fibrotic drug, nintedanib, inhibited YAP and showed anti-fibrotic effects. CONCLUSIONS: This is the first report that in vivo injection of collagenase into uterine fibroids led to a reduction in Hippo/YAP signaling and crucial genes and pathways involved in fibroid growth. These results indicate that targeting ECM stiffness and Hippo signaling might be an effective strategy for uterine fibroids.

Human Pharmacokinetics and Safety of Subcutaneous Collagenase Clostridium Histolyticum in Women.

BACKGROUND: Clostridium collagenase histolyticum (CCH) is being evaluated in women as a cellulite treatment. OBJECTIVE: To report preclinical safety and human pharmacokinetics (PK) and safety data for CCH. METHODS: Across 3 PK studies, 41 women received 12 subcutaneous injections per thigh/buttock in 1 session (up to 3.36 mg/dose). Blood samples were taken at baseline; at 5, 10, 20, and 30 minutes postdose; and at 1, 2, 4, 8, 12, 24, 48, 168, and 504 hours postdose. In a preclinical study, rats received 0, 0.029, 0.13, or 0.29 mg/dose of CCH intravenously (IV) every other day (QOD) for 16 days (total, 8 doses) and were evaluated for histopathologic changes. RESULTS: In human PK studies, no quantifiable plasma concentrations of AUX-I or AUX-II were observed postdose (n= 39 evaluable). Adverse events were injection site–related (bruising [97.6%], pain [87.8%], and edema/swelling [46.3%]). Antidrug antibodies were seen in most women at 504 hours postdose. In rats, plasma concentrations of AUX-I and AUX-II (CCH components) were measurable for 30 minutes and 1-2 hours, respectively, after IV administration. At ≥43× proposed human therapeutic dose on a mg/kg basis, rats experienced elevated liver enzyme levels, increased liver weights, and histologic changes that were mostly reversed during a 14-day recovery period. CONCLUSIONS: In human studies, no quantifiable circulating CCH levels were observed after a single subcutaneous dose of CCH up to 3.36 mg. Preclinical data indicated that repeat IV dosing (QOD; 8 doses) at ≥43× proposed human dose on a mg/kg basis for CCH was generally well tolerated.J Drugs Dermatol. 2020;19(9):852-856. doi:10.36849/JDD.2020.5048THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Insights Into the Pathophysiology of Cellulite: A Review.

BACKGROUND: The etiology of cellulite is unclear. Treatment of cellulite has targeted adipose tissue, dermis, and fibrous septae with varying degrees of success and durability of response. OBJECTIVE: Results from clinical trials that target different anatomical aspects of cellulite can provide insights into the underlying pathophysiology of cellulite. MATERIALS AND METHODS: A search of the PubMed database and ClinicalTrials.gov website was conducted to identify clinical trials that have investigated treatments for cellulite. RESULTS: A lack of trial protocol standardization, objective means for quantification of improvement and reported cellulite severity, and short-term follow-up, as well as variation in assessment methods have made comparisons among efficacy studies challenging. However, the lack of durable efficacy and inconsistency seen in clinical results suggest that dermal or adipose tissue changes are not the primary etiologies of cellulite. Clinical studies targeting the collagen-rich fibrous septae in cellulite dimples through mechanical, surgical, or enzymatic approaches suggest that targeting fibrous septae is the strategy most likely to provide durable improvement of skin topography and the appearance of cellulite. CONCLUSION: The etiology of cellulite has not been completely elucidated. However, there is compelling clinical evidence that fibrous septae play a central role in the pathophysiology of cellulite.

Development of Collagenase Treatment for Dupuytren Disease.

Proof-of-principle, basic-science studies, using a rat-tail tendon model and surgically removed Dupuytren cords, began collagenase Clostridium histolyticum (CCH) development. Clinical studies in humans were then conducted, where the primary endpoint was reduction in contracture to within 0° to 5° of extension. Phase 2 studies, which confirmed the optimal dose of collagenase as 0.58 mg, showed injectable CCH reduced contractures in MP and PIP joints to within 0° to 5° in many joints and was well tolerated. Clinical results from phase 3 studies confirmed the efficacy and safety of injectable CCH as a viable nonsurgical intervention.

Anesthesia for collagenase clostridium histolyticum injection in patients with dupuytren disease: A cohort analysis.

Procedural pain is one of the most common adverse effects reported by patients with Dupuytren disease (DD) treated with collagenase clostridium histolyticum (CCH). The aim of this study was to assess the effectiveness of wrist block before CCH injection in reducing procedural pain and to analyze its impact on adverse effects. We performed a prospective, single-center study in which we compared two groups of patients in a consecutive cohort. In the first group (NO-BLOCK), wrist block was only performed before finger extension, whereas in the second group (BLOCK), it was performed before CCH injection and finger extension. Pain was assessed on a 10-item numerical rating scale. Our results show that pain scores were clearlylower in the BLOCK group than in the NO-BLOCK group: 4.72 vs. 0.61 for CCH injection and 3.43 vs. 0.82 for finger extension. Patients who rated CCH injection pain with a score of 4 or higher were 11 times more likely to experience pain during extension. There was a weak correlation between the use of wrist block for CCH injection and the occurrence of skin lacerations (Spearman's rho = -0.222, p < 0.01) and the presence of pruritus (Spearman's rho = 0.183, p < 0.07). In conclusion, wrist block before CCH injection is an effective measure of decreasing perceived pain throughout the different stages of CCH treatment in patients with DD.

Update on management of diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are a serious complication of diabetes that results in significant morbidity and mortality. Mortality rates associated with the development of a DFU are estimated to be 5% in the first 12 months, and 5-year morality rates have been estimated at 42%. The standard practices in DFU management include surgical debridement, dressings to facilitate a moist wound environment and exudate control, wound off-loading, vascular assessment, and infection and glycemic control. These practices are best coordinated by a multidisciplinary diabetic foot wound clinic. Even with this comprehensive approach, there is still room for improvement in DFU outcomes. Several adjuvant therapies have been studied to reduce DFU healing times and amputation rates. We reviewed the rationale and guidelines for current standard of care practices and reviewed the evidence for the efficacy of adjuvant agents. The adjuvant therapies reviewed include the following categories: nonsurgical debridement agents, dressings and topical agents, oxygen therapies, negative pressure wound therapy, acellular bioproducts, human growth factors, energy-based therapies, and systemic therapies. Many of these agents have been found to be beneficial in improving wound healing rates, although a large proportion of the data are small, randomized controlled trials with high risks of bias.

Clostridial collagenase ointment and medicinal honey utilization for pressure ulcers in US hospitals.

AIMS: To describe the utilization of clostridial collagenase ointment (CCO) and medicinal honey debridement methods in real-world inpatient and outpatient hospital settings among pressure ulcer (PU) patients and compare the frequency of healthcare re-encounters between CCO- and medicinal honey-treated patients. MATERIALS AND METHODS: De-identified hospital discharge records for patients receiving CCO or medicinal honey methods of debridement and having an ICD-9 code for PU were extracted from the US Premier Healthcare Database. Multivariable analysis was used to compare the frequency of inpatient and outpatient revisits up to 6 months after an index encounter for CCO- vs medicinal honey-treated PUs. RESULTS: The study identified 48,267 inpatients and 2,599 outpatients with PUs treated with CCO or medicinal honeys. Among study inpatients, n = 44,725 (93%) were treated with CCO, and n = 3,542 (7%) with medicinal honeys. CCO and medicinal honeys accounted for 1,826 (70%) and 773 (30%), respectively, of study outpatients. In adjusted models, those treated with CCO had lower odds for inpatient readmissions (OR = 0.86, 95% CI = 0.80-0.94) after inpatient index visits, and outpatient re-encounters both after inpatient (OR = 0.73, 95% CI = 0.67-0.79) and outpatient (OR = 0.78, 95% CI = 0.64-0.95) index visits in 6 months of follow-up. LIMITATIONS: The study was observational in nature, and did not adjust for reasons why patients were hospitalized initially, or why they returned to the facility. Although the study adjusted for differences in a variety of demographic, clinical, and hospital characteristics between the treatments, we are not able to rule out selection bias. CONCLUSION: Patients with CCO-treated PUs returned to inpatient and outpatient hospital settings less often compared with medicinal honey-treated PUs. These results from real-world administrative data help to gain a better understanding of the clinical characteristics of patients with PUs treated with these two debridement methods and the economic implications of debridement choice in the acute care setting.

Injectable collagenase Clostridium histolyticum as a nonsurgical treatment for Dupuytren's disease.

OBJECTIVE: Nonsurgical treatment of Dupuytren's disease using collagenase Clostridium histolyticum (CCH). INDICATIONS: Metacarpophalangeal (MP) joint (20-100°) and proximal interphalangeal (PIP) joint (20-80°) contractures. CONTRAINDICATIONS: Pregnancy, previous hypersensitivity to collagenase or excipients, anticoagulant use within 7 days prior to treatment. INJECTION TECHNIQUE: CCH injected directly into the Dupuytren's cord weakening the contracted cord. After injection, the patient returns the following day to allow CCH to lyse the collagen within the cord. An extension force is then applied to the involved finger to disrupt the weakened cord. POSTMANIPULATION MANAGEMENT: Use of extension splint at night, movement instructions during the day. RESULTS: A total of 120 patients (107 men; 13 women; mean age 62 years, range 30-84 years) were treated. In 49% the little finger, in 44% the ring finger, in 4% the middle finger, and in 3% the index finger was treated. Full release was achieved in 71%, partial release in 26%, and no change in 3% of patients. The median pretreatment contracture for the MP joint was 37° (range 25-100°) and PIP joint 51° (range 30-97°). At 12 months, the mean contracture for the MP joint was 9° (range 0-25°) and for the PIP joint 21° (range 10-36°). Adverse events observed in 96% of patients for 3 months . No tendon ruptures, anaphylactic reactions, or nerve or ligament injuries observed.

Inhibition of Collagenase by Mycosporine-like Amino Acids from Marine Sources.

Matrix metalloproteinases play an important role in extracellular matrix remodeling. Excessive activity of these enzymes can be induced by UV light and leads to skin damage, a process known as photoaging. In this study, we investigated the collagenase inhibition potential of mycosporine-like amino acids, compounds that have been isolated from marine organisms and are known photoprotectants against UV-A and UV-B. For this purpose, the commonly used collagenase assay was optimized and for the first time validated in terms of relationships between enzyme-substrate concentrations, temperature, incubation time, and enzyme stability. Three compounds were isolated from the marine red algae Porphyra sp. and Palmaria palmata, and evaluated for their inhibitory properties against Chlostridium histolyticum collagenase. A dose-dependent, but very moderate, inhibition was observed for all substances and IC50 values of 104.0 µM for shinorine, 105.9 µM for porphyra, and 158.9 µM for palythine were determined. Additionally, computer-aided docking models suggested that the mycosporine-like amino acids binding to the active site of the enzyme is a competitive inhibition.

Addition of Grape Seed Extract Renders Phosphoric Acid a Collagen-stabilizing Etchant.

Previous studies found that grape seed extract (GSE), which is rich in proanthocyanidins, could protect demineralized dentin collagen from collagenolytic activities following clinically relevant treatment. Because of proanthocyanidin's adverse interference to resin polymerization, it was believed that GSE should be applied and then rinsed off in a separate step, which in effect increases the complexity of the bonding procedure. The present study aimed to investigate the feasibility of combining GSE treatment with phosphoric acid etching to address the issue. It is also the first attempt to formulate collagen-cross-linking dental etchants. Based on Fourier-transformed infrared spectroscopy and digestion assay, it was established that in the presence of 20% to 5% phosphoric acid, 30 sec of GSE treatment rendered demineralized dentin collagen inert to bacterial collagenase digestion. Based on this positive result, the simultaneous dentin etching and collagen protecting of GSE-containing phosphoric acid was evaluated on the premise of a 30-second etching time. According to micro-Raman spectroscopy, the formulation containing 20% phosphoric acid was found to lead to overetching. Based on scanning and transmission electronic microscopy, this same formulation exhibited unsynchronized phosphoric acid and GSE penetration. Therefore, addition of GSE did render phosphoric acid a collagen-stabilizing etchant, but the preferable phosphoric acid concentration should be <20%.

Resource utilisation associated with single digit Dupuytren's contracture treated with either surgery or injection of collagenase Clostridium histolyticum.

UNLABELLED: The gold standard treatment for Dupuytren's contracture is surgical excision of the cord. A non-surgical treatment with collagenase clostridium histolyticum injection is available but appears costly. OBJECTIVES: To provide data on resource consumption related to surgical and non-surgical treatment for Dupuytren's contracture. DESIGN AND PARTICIPANTS: Twenty patients with a single digit Dupuytren's contracture, 10 treated with surgical excision, and 10 treated with a single injection of collagenase. MEASUREMENTS: Minutes spent in theatre, number of follow-up appointments, time to skin healing, and patients return to normal activities of daily living. RESULTS: The injection group was significantly better regarding theatre time (p < 0.0001), follow-up appointments (p = 0.048), skin healing time (p < 0.001), and return to normal activities of daily living (p = 0.02) than the operated group. CONCLUSIONS: There are significant personal and health economic differences between the two methods of treatment which may influence local choice.

Efficacy and tolerability of Day 2 manipulation and local anaesthesia after collagenase injection in patients with Dupuytren's contracture.

In clinical trials, treating Dupuytren's contracture with collagenase injection involves manipulation the day after injection, without local anaesthesia. We evaluated the efficacy and tolerability of manipulation 2 days after injection with local anaesthesia. Forty-five patients received 50 injections into cords contracting metacarpophalangeal and proximal interphalangeal joints; follow-up visits were at 3 and 14 weeks. For the metacarpophalangeal joints there were >90% reduction in contracture at both visits. The proximal interphalangeal joints that improved spontaneously after metacarpophalangeal injection or received direct injections showed 51-55% reduction in contracture. Changes in scores on the Patient Evaluation Measure suggest that patients perceived improvements in their hand function was good and they were satisfied with the procedure. Collagenase and local anaesthesia injections were well tolerated; adverse events were localized to the injection site and were mild and transient in nature. These findings provide another viable option for practising surgeons and may help with the logistics of patient care.

Baicalin attenuates brain edema in a rat model of intracerebral hemorrhage.

Baicalin is a flavonoid compound purified from the roots of Scutellaria baicalensis, which possesses multiple biological activities. Previous studies have shown that baicalin is protective in ischemic cerebral diseases. The aim of the present study was to examine the effects of baicalin on brain injury in a rat model of intracerebral hemorrhage (ICH) and to explore the possible mechanisms. Intracerebral hemorrhage was induced in male Wistar rats by injection of 0.5 U collagenaseVII to the caudate nucleus. Sham operation rats were injected with equal volume of saline. After the induction of ICH, the rats were randomly divided into four groups and administered with different dose of baicalin (0, 25, 50, or 100 mg/kg in saline) through peritoneal injection. The brain tissues around the hemorrhage areas were collected on days 1, 3, and 5 after treatment. Brain edema was analyzed by desiccation method; the metalloproteinase-9 (MMP-9) protein and mRNA expression were determined by western blotting and real time RT-PCR, respectively. Nuclear factor-κB (NF-κB) protein expression was analyzed by western blotting. IL-1ß and IL-6 levels were determined by enzyme-linked immunosorbent assay. Blood-brain barrier permeability was determined by Evans blue leakage method. The results showed that baicalin reduced brain edema following ICH in a dose-dependent manner, with concomitant inhibition of NF-κB activation and suppression of MMP-9 expression. In addition, baicalin also reduced IL-1ß and IL-6 production, as well as blood-brain barrier permeability. The above results indicated that baicalin prevents against perihematomal edema development after intracerebral hemorrhage possibly through an anti-inflammatory mechanism.

Use of resources and costs associated with the treatment of Dupuytren's contracture at an orthopedics and traumatology surgery department in Denia (Spain): collagenase clostridium hystolyticum versus subtotal fasciectomy.

BACKGROUND: Our purpose was to analyze and compare the use of direct health resources and costs generated in the treatment of Dupuytren's contracture using two different techniques: subtotal fasciectomy and infiltration with Collagenase Clostridium Histolyticum (CCH) in regular clinical practice at the Orthopedic and Traumatology Surgery (OTS) Department at the Hospital de Denia (Spain). METHODS: Observational, retrospective study based on data from the computerized clinical histories of two groups of patients- those treated surgically using a one or two digit subtotal fasciectomy technique (FSC) and those treated with CCH infiltration, monitored in regular clinical practice from February, 2009 to May, 2012. Demographic (age, sex), clinical (number of digits affected and which ones) and use of resources (hospitalizations, medical visits, tests and drugs) data were collected. Resource use and associated costs, according to the hospital's accounting department, were compared based on the type of treatment from Spain's National Health Service. RESULTS: 91 patients (48 (52.8%) in the FSC group) were identified. The average age and number of digits affected was 65.9 (9.2) years and 1.33 (0.48) digits affected in the FSC group, and 65.1 (9.7) years and 1.16 (0.4) digits in the CCH group.Overall, the costs of treating Dupuytren's disease with subtotal FSC amount to €1,814 for major ambulatory surgery and €1,961 with hospital stay including admission, surgical intervention (€904), examinations, dressings and physiotherapy. As to collagenase infiltration, costs amount to €952 (including minor surgery admission, vial with product, office examination and dressings). Finally, comparing total costs for treatments, a savings of €388 is estimated in favor of CCH treatment in the best-case scenario (patient under MAS system with no need for physiotherapy) and €1,008 in the worst-case scenario (patient admitted to hospital needing subsequent physiotherapy), implying a savings of 29% and 51%, respectively. CONCLUSIONS: This study demonstrates that treating patients with DC by injection with CCH at the OTS department of the Hospital de Denia generates a total savings of 29% and 51% (€388 and €1008) compared with fasciectomy at the time of treatment. Long term evolution of CCH treatment is uncertain and the recurrence rate unknown.

Cranberry proanthocyanidins act in synergy with licochalcone A to reduce Porphyromonas gingivalis growth and virulence properties, and to suppress cytokine secretion by macrophages.

AIMS: Periodontitis is an inflammatory disease of polymicrobial origin that affects the tooth-supporting tissues. With the spread of antibiotic resistance among pathogenic bacteria, alternative strategies are required to better control infectious diseases such as periodontitis. The aim of our study was to investigate whether two natural compounds, A-type cranberry proanthocyanidins (AC-PACs) and licochalcone A, act in synergy against Porphyromonas gingivalis and the host inflammatory response of a macrophage model. METHODS AND RESULTS: Using a checkerboard microtitre test, AC-PACs and licochalcone A were found to act in synergy to inhibit P. gingivalis growth and biofilm formation. Fluorescein isothiocyanate-labelled P. gingivalis adhesion to oral epithelial cells was also inhibited by a combination of the two natural compounds in a synergistic manner. Fluorometric assays showed that although AC-PACs and licochalcone A reduced both MMP-9 and P. gingivalis collagenase activities, no synergy was obtained with a combination of the compounds. Lastly, AC-PACs and licochalcone A also acted in synergy to reduce the lipopolysaccharide (LPS)-induced secretion of the pro-inflammatory mediators IL-1ß, TNF-α, IL-6 and IL-8 in a macrophage model. CONCLUSIONS: A-type cranberry proanthocyanidins and licochalcone A, natural compounds from cranberry and licorice, respectively, act in synergy on both P. gingivalis and the host immune response, the two principal etiological factors of periodontitis. SIGNIFICANCE AND IMPACT OF THE STUDY: The combined use of AC-PACs and licochalcone A may be a potential novel therapeutic strategy for the treatment and prevention of periodontal disease.

Protective effect of Withania somnifera and Cardiospermum halicacabum extracts against collagenolytic degradation of collagen.

The irreversible destruction of extracellular matrix (ECM) such as cartilage, tendon, and bone that comprise synovial joints is the hallmark of both rheumatoid arthritis and osteoarthritis by over-expression of matrix metalloproteinase (MMP)-collagenases. We report herein the detailed study on the inhibitory effects of Withania somnifera extract (WSE) and Cardiospermum halicacabum extract (CHE) on Clostridium histolyticum collagenase (ChC) activity against the degradation of the ECM component of bovine Achilles tendon type I collagen by hydroxyproline assay method. Interaction of WSE and CHE with ChC exhibited 71% and 88% inhibition, respectively, to the collagenolytic activity of ChC against collagen degradation, and the inhibition was found to be concentration-dependent. The inhibition kinetics of ChC by both the extracts has been deduced from the extent of hydrolysis of N-[3-(2-furyl) acryloyl]-Leu-Gly-Pro-Ala. Both WSE and CHE are provided competitive and mixed type inhibition on ChC activity, respectively. Circular dichroism studies of ChC on treatment with WSE and CHE revealed changes in the secondary structure of collagenase. These results suggest that the WSE and CHE facilitated collagen stabilization through collagenase inhibition.