In Vitro Superparamagnetic Hyperthermia Employing Magnetite Gamma-Cyclodextrin Nanobioconjugates for Human Squamous Skin Carcinoma Therapy.

In vitro alternative therapy of human epidermoid squamous carcinoma (A431) by superparamagnetic hyperthermia (SPMHT) using Fe3O4 (magnetite) superparamagnetic nanoparticles (SPIONs) with an average diameter of 15.8 nm, bioconjugated with hydroxypropyl gamma-cyclodextrins (HP-γ-CDs) by means of polyacrylic acid (PAA) biopolymer, is presented in this paper. The therapy was carried out at a temperature of 43 °C for 30 min using the concentrations of Fe3O4 ferrimagnetic nanoparticles from nanobioconjugates of 1, 5, and 10 mg/mL nanoparticles in cell suspension, which were previously found by us to be non-toxic for healthy cells (cell viabilities close to 100%), according to ISO standards (cell viability must be greater than 70%). The temperature for the in vitro therapy was obtained by the safe application (without exceeding the biological limit and cellular damage) of an alternating magnetic field with a frequency of 312.4 kHz and amplitudes of 168, 208, and 370 G, depending on the concentration of the magnetic nanoparticles. The optimal concentration of magnetic nanoparticles in suspension was found experimentally. The results obtained after the treatment show its high effectiveness in destroying the A431 tumor cells, up to 83%, with the possibility of increasing even more, which demonstrates the viability of the SPMHT method with Fe3O4-PAA-(HP-γ-CDs) nanobioconjugates for human squamous cancer therapy.

Lactiplantibacillus plantarum Induces Apoptosis in Melanoma and Breast Cancer Cells.

Despite the notable advancements witnessed in the past decade in medical and health research domain, cancer remains a prominent global cause of mortality. Moreover, the conventional treatments employed to combat this disease have been found to considerably compromise the quality of life experienced by patients due to its severe side effects. Recent in vitro studies revealed encouraging findings on the potential beneficial effects of probiotics as adjuvants of anticancer therapy, and even as possible agents for the prevention and treatment of various types of malignancies. From this standpoint, the primary objective of this work was to investigate the anticancer properties of Lactiplantibacillus plantarum (LP) and elucidate its underlying mechanism of action. In order to investigate this matter, several doses of LP (ranging from 105 to 1010 CFU/mL) were examined in relation to melanoma cancer cell lines (A375) and breast cancer cell line (MCF-7). The cell viability findings, which were substantiated by morphological investigations and annexin V/PI assay, indicated that LP exerted inhibitory effects on cellular activity and triggered apoptosis. Additionally, upon further investigation into its mechanism, it was observed through the apoptosis assay and Western blot analysis that the administration of LP resulted in an elevation of pro-apoptotic BAX protein levels and an upregulation of cleaved poly-ADP-ribose polymerase (PARP) protein expression. Conversely, the levels of anti-apoptotic Bcl-2 protein were found to decrease in the A375 and MCF-7 cell lines. These findings provide insight into the pro-apoptotic mechanism of action of LP in these specific cell lines.

Newly Synthesized CoFe2-xDyxO4 (x = 0; 0.1; 0.2; 0.4) Nanoparticles Reveal Promising Anticancer Activity against Melanoma (A375) and Breast Cancer (MCF-7) Cells.

The current study focuses on the synthesis via combustion of dysprosium-doped cobalt ferrites that were subsequently physicochemically analyzed in terms of morphological and magnetic properties. Three types of doped nanoparticles were prepared containing different Dy substitutions and coated with HPGCD for higher dispersion properties and biocompatibility, and were later submitted to biological tests in order to reveal their potential anticancer utility. Experimental data obtained through FTIR, XRD, SEM and TEM confirmed the inclusion of Dy3+ ions in the nanoparticles' structure. The size of the newly formed nanoparticles ranged between 20 and 50 nm revealing an inverse proportional relationship with the Dy content. Magnetic studies conducted by VSM indicated a decrease in remanent and saturation mass magnetization, respectively, in Dy-doped nanoparticles in a direct proportionality with the Dy content; the decrease was further amplified by cyclodextrin complexation. Biological assessment in the presence/absence of red light revealed a significant cytotoxic activity in melanoma (A375) and breast (MCF-7) cancer cells, while healthy keratinocytes (HaCaT) remained generally unaffected, thus revealing adequate selectivity. The investigation of the underlying cytotoxic molecular mechanism revealed an apoptotic process as indicated by nuclear fragmentation and shrinkage, as well as by Western blot analysis of caspase 9, p53 and cyclin D1 proteins. The anticancer activity for all doped Co ferrites varied was in a direct correlation to their Dy content but without being affected by the red light irradiation.

The Influence of an Isocyanate Structure on a Polyurethane Delivery System for 2'-Deoxycytidine-5'-monophosphate.

The delivery of nucleosides represents an interesting research trend in recent years due to their application in various viral infections. The main aims of this study were to develop and to characterize polyurethane particles that are intended to be used for the transport of nucleosides. Three samples have been prepared using aliphatic diisocyanates, a mixture of polyethylene glycol, polycaprolactone, and diols, respectively. The samples were characterized through refractivity measurements, drug loading efficacy, release and penetration rate investigations, FTIR and Raman spectroscopy, thermal analyses, Zetasizer, SEM, HDFa cells viability, and irritation tests on mice skin. The results indicate the obtaining of particles with sizes between 132 and 190 nm, positive Zeta potential values (28.3-31.5 mV), and a refractivity index around 1.60. A good thermal stability was found, and SEM images show a medium tendency to agglomerate. The samples' color, pH, and electrical conductivity have changed only to a small extent over time, and the evaluations indicate an almost 70% encapsulation efficacy, a prolonged release, and that around 70% of particles have penetrated an artificial membrane in the first 24 h. The synthesized products should be tested in further clinical trials, and the current tests on cell cultures and mice skin revealed no side effects.

Novel Triterpenic Acid-Benzotriazole Esters Act as Pro-Apoptotic Antimelanoma Agents.

Pentacyclic triterpenes, such as betulinic, ursolic, and oleanolic acids are efficient and selective anticancer agents whose underlying mechanisms of action have been widely investigated. The introduction of N-bearing heterocycles (e.g., triazoles) into the structures of natural compounds (particularly pentacyclic triterpenes) has yielded semisynthetic derivatives with increased antiproliferative potential as opposed to unmodified starting compounds. In this work, we report the synthesis and biological assessment of benzotriazole esters of betulinic acid (BA), oleanolic acid (OA), and ursolic acid (UA) (compounds 1-3). The esters were obtained in moderate yields (28-42%). All three compounds showed dose-dependent reductions in cell viability against A375 melanoma cells and no cytotoxic effects against healthy human keratinocytes. The morphology analysis of treated cells showed characteristic apoptotic changes consisting of nuclear shrinkage, condensation, fragmentation, and cellular membrane disruption. rtPCR analysis reinforced the proapoptotic evidence, showing a reduction in anti-apoptotic Bcl-2 expression and upregulation of the pro-apoptotic Bax. High-resolution respirometry studies showed that all three compounds were able to significantly inhibit mitochondrial function. Molecular docking showed that compounds 1-3 showed an increase in binding affinity against Bcl-2 as opposed to BA, OA, and UA and similar binding patterns compared to known Bcl-2 inhibitors.

Antimicrobial activity, in vitro anticancer effect (MCF-7 breast cancer cell line), antiangiogenic and immunomodulatory potentials of Populus nigra L. buds extract.

PURPOSE: The aim of this study was to evaluate the antioxidant potential, antimicrobial activity, the in vitro anticancer effect (tested on MCF-7 breast cancer cell line), as well as the antiangiogenic and immunomodulatory potential of Populus nigra L. bud (Pg) extract collected from the western part of Romania. RESULTS: Populus nigra L. bud extract presents an important antioxidant activity, due to the rich phytochemical composition. Regarding the biological activity, results have shown that poplar bud extract presents a significant inhibitory activity against Gram-positive bacteria and a dose-dependent decrease of MCF-7 tumor cell viability with an IC50 of 66.26 µg/mL, while not affecting healthy cells. Phenomena of early apoptotic events at the maximum concentration tested (150 µg/mL) were detected by Annexin V-PI double staining. The extract induced G0/G1 phase cell cycle arrest. In addition, Pg extract showed antiangiogenic potential on the chorioallantoic membrane. Also, at the highest concentration (150 µg/mL), good tolerability and no signs of toxicity upon vascular plexus were observed. Moreover, in low concentrations, the Pg extract had immunomodulatory activity on primary human dendritic cells by upregulating IL-12 and IL-23 subunits. CONCLUSION: The study concludes that poplar bud extract elicited antioxidant activity, antitumor properties on the breast cancer cell line, followed by an antiangiogenic effect and an immunomodulatory potential on human primary dendritic cells. The biological activity of Populus nigra L. buds extract may open new directions of research on the topic addressed.

The Optimized Delivery of Triterpenes by Liposomal Nanoformulations: Overcoming the Challenges.

The last decade has witnessed a sustained increase in the research development of modern-day chemo-therapeutics, especially for those used for high mortality rate pathologies. However, the therapeutic landscape is continuously changing as a result of the currently existing toxic side effects induced by a substantial range of drug classes. One growing research direction driven to mitigate such inconveniences has converged towards the study of natural molecules for their promising therapeutic potential. Triterpenes are one such class of compounds, intensively investigated for their therapeutic versatility. Although the pharmacological effects reported for several representatives of this class has come as a well-deserved encouragement, the pharmacokinetic profile of these molecules has turned out to be an unwelcomed disappointment. Nevertheless, the light at the end of the tunnel arrived with the development of nanotechnology, more specifically, the use of liposomes as drug delivery systems. Liposomes are easily synthesizable phospholipid-based vesicles, with highly tunable surfaces, that have the ability to transport both hydrophilic and lipophilic structures ensuring superior drug bioavailability at the action site as well as an increased selectivity. This study aims to report the results related to the development of different types of liposomes, used as targeted vectors for the delivery of various triterpenes of high pharmacological interest.

The Role of Cyclodextrins in the Design and Development of Triterpene-Based Therapeutic Agents.

Triterpenic compounds stand as a widely investigated class of natural compounds due to their remarkable therapeutic potential. However, their use is currently being hampered by their low solubility and, subsequently, bioavailability. In order to overcome this drawback and increase the therapeutic use of triterpenes, cyclodextrins have been introduced as water solubility enhancers; cyclodextrins are starch derivatives that possess hydrophobic internal cavities that can incorporate lipophilic molecules and exterior surfaces that can be subjected to various derivatizations in order to improve their biological behavior. This review aims to summarize the most recent achievements in terms of triterpene:cyclodextrin inclusion complexes and bioconjugates, emphasizing their practical applications including the development of new isolation and bioproduction protocols, the elucidation of their underlying mechanism of action, the optimization of triterpenes' therapeutic effects and the development of new topical formulations.

Effects of Cadmium Sulfate on the Brown Garden Snail Cornu aspersum: Implications for DNA Methylation.

An extensive literature exists regarding the cellular, physiological, and genetic effects of cadmium (Cd)-A highly toxic, but commonly used trace metal in modern industry. However, limited data are available on its epigenetic effects, especially for terrestrial sentinel invertebrates. We determined Cd retention, total DNA methylation, and the methylation status of 5' end of the Cd-MT gene in the hepatopancreas of the brown garden snail, Cornu aspersum, fed Cd sulfate for four weeks. Bodyweight changes and survival were also measured. Hepatopancreas cadmium increased in a dose-dependent manner from the third-lowest dose onward, with very large amounts being found for the highest treatment group. However, no mortalities occurred, irrespective of dietary Cd dose. We identified significant genome-wide hypermethylation in specimens given the highest dose, which overlapped with a significant bodyweight decrease. The Cd-MT gene showed an unmethylated 5' end of the Cd-MT gene and this status was not affected by cadmium exposure. Hepatopancreas DNA methylation is as sensitive as bodyweight to non-lethal concentrations of dietary Cd given as cadmium sulfate but less responsive than tissue accumulation. Such an exposure event, by contrast, does not affect the methylation status of the Cd-MT gene 5' end.

Vegetal Compounds as Sources of Prophylactic and Therapeutic Agents in Dentistry.

Dental pathology remains a global health problem affecting both children and adults. The most important dental diseases are dental caries and periodontal pathologies. The main cause of oral health problems is overpopulation with pathogenic bacteria and for this reason, conventional therapy can often be ineffective due to bacterial resistance or may have unpleasant side effects. For that reason, studies in the field have focused on finding new therapeutic alternatives. Special attention is paid to the plant kingdom, which offers a wide range of plants and active compounds in various pathologies. This review focused on the most used plants in the dental field, especially on active phytocompounds, both in terms of chemical structure and in terms of mechanism of action. It also approached the in vitro study of active compounds and the main types of cell lines used to elucidate the effect and mechanism of action. Thus, medicinal plants and their compounds represent a promising and interesting alternative to conventional therapy.

Assessment of Betulinic Acid Cytotoxicity and Mitochondrial Metabolism Impairment in a Human Melanoma Cell Line.

Melanoma represents one of the most aggressive and drug resistant skin cancers with poor prognosis in its advanced stages. Despite the increasing number of targeted therapies, novel approaches are needed to counteract both therapeutic resistance and the side effects of classic therapy. Betulinic acid (BA) is a bioactive phytocompound that has been reported to induce apoptosis in several types of cancers including melanomas; however, its effects on mitochondrial bioenergetics are less investigated. The present study performed in A375 human melanoma cells was aimed to characterize the effects of BA on mitochondrial bioenergetics and cellular behavior. BA demonstrated a dose-dependent inhibitory effect in both mitochondrial respiration and glycolysis in A375 melanoma cells and at sub-toxic concentrations (10 µM) induced mitochondrial dysfunction by eliciting a decrease in the mitochondrial membrane potential and changes in mitochondria morphology and localization. In addition, BA triggered a dose-dependent cytotoxic effect characterized by apoptotic features: morphological alterations (nuclear fragmentation, apoptotic bodies) and the upregulation of pro-apoptotic markers mRNA expression (Bax, Bad and Bak). BA represents a viable therapeutic option via a complex modulatory effect on mitochondrial metabolism that might be useful in advanced melanoma or as reliable strategy to counteract resistance to standard therapy.

Integrating Ethnobotany, Phytochemistry, and Pharmacology of Cotinus coggygria and Toxicodendron vernicifluum: What Predictions can be Made for the European Smoketree?

The smoketree (Cotinus coggygria) is a historically known medicinal plant from Southeast Europe. Its ethnomedicinal use in skin and mucosal lesions is commonly accepted across countries. Other utilizations reported locally include fever reduction, cardiac diseases, hypertension, urinary diseases, cough, asthma, hemorrhoids, diabetes, numbness of arm, liver disease, and cancer. Departing from the smoketree's traditional uses, this review summarizes investigations on the phytochemistry and bioactivity of the plant. In vitro and in vivo experiments supporting wound-healing, anti-inflammatory, antibacterial, cytotoxic, antioxidative, hepatoprotective, and antidiabetic effects are presented. Metabolites from smoketree that are responsible for the main pharmacological effects of smoketree are pointed out. Furthermore, the review performs a comparison between C. coggygria and the lacquer tree (Toxicodendron vernicifluum). The latter is a comprehensively studied species used in Asian phytotherapy, with whom the European smoketree shares a consistent pool of secondary metabolites. The comparative approach aims to open new perspectives in the research of smoketree and anticipates an optimized use of C. coggygria in therapy. It also points out the relevance of a chemosystematic approach in the field of medicinal plants research.

Anticancer Potential of Betulonic Acid Derivatives.

Clinical trials have evidenced that several natural compounds, belonging to the phytochemical classes of alkaloids, terpenes, phenols and flavonoids, are effective for the management of various types of cancer. Latest research has proven that natural products and their semisynthetic variants may serve as a starting point for new drug candidates with a diversity of biological and pharmacological activities, designed to improve bioavailability, overcome cellular resistance, and enhance therapeutic efficacy. This review was designed to bring an update regarding the anticancer potential of betulonic acid and its semisynthetic derivatives. Chemical derivative structures of betulonic acid including amide, thiol, and piperidine groups, exert an amplification of the in vitro anticancer potential of betulonic acid. With the need for more mechanistic and in vivo data, some derivatives of betulonic acids may represent promising anticancer agents.

Antibiotics: Conventional Therapy and Natural Compounds with Antibacterial Activity-A Pharmaco-Toxicological Screening.

Antibiotics are considered as a cornerstone of modern medicine and their discovery offers the resolution to the infectious diseases problem. However, the excessive use of antibiotics worldwide has generated a critical public health issue and the bacterial resistance correlated with antibiotics inefficiency is still unsolved. Finding novel therapeutic approaches to overcome bacterial resistance is imperative, and natural compounds with antibacterial effects could be considered a promising option. The role played by antibiotics in tumorigenesis and their interrelation with the microbiota are still debatable and are far from being elucidated. Thus, the present manuscript offers a global perspective on antibiotics in terms of evolution from a historical perspective with an emphasis on the main classes of antibiotics and their adverse effects. It also highlights the connection between antibiotics and microbiota, focusing on the dual role played by antibiotics in tumorigenesis. In addition, using the natural compounds with antibacterial properties as potential alternatives for the classical antibiotic therapy is discussed.

Melissa officinalis L. Aqueous Extract Exerts Antioxidant and Antiangiogenic Effects and Improves Physiological Skin Parameters.

Melissa officinalis (MO) is a medicinal plant well-known for its multiple pharmacological effects, including anti-inflammatory, anticancer and beneficial effects on skin recovery. In this context, the present study was aimed to investigate the in vitro and in vivo safety profile of an MO aqueous extract by assessing cell viability on normal (HaCaT-human keratinocytes) and tumor (A375-human melanoma) cells and its impact on physiological skin parameters by a non-invasive method. In addition, the antioxidant activity and the antiangiogenic potential of the extract were verified. A selective cytotoxic effect was noted in A375 cells, while no toxicity was noticed in healthy cells. The MO aqueous extract safety profile after topical application was investigated on SKH-1 mice, and an enhanced skin hydration and decreased erythema and transepidermal water loss levels were observed. The in ovo CAM assay, performed to investigate the potential modulating effect on the angiogenesis process and the blood vessels impact, indicated that at concentrations of 100 and 500 µg/mL, MO aqueous extract induced a reduction of thin capillaries. No signs of vascular toxicity were recorded at concentrations as high as 1000 µg/mL. The aqueous extract of MO leaves can be considered a promising candidate for skin disorders with impaired physiological skin parameters.

Plant-Derived Anticancer Compounds as New Perspectives in Drug Discovery and Alternative Therapy.

Despite the recent advances in the field of chemically synthetized pharmaceutical agents, nature remains the main supplier of bioactive molecules. The research of natural products is a valuable approach for the discovery and development of novel biologically active compounds possessing unique structures and mechanisms of action. Although their use belongs to the traditional treatment regimes, plant-derived compounds still cover a large portion of the current-day pharmaceutical agents. Their medical importance is well recognized in the field of oncology, especially as an alternative to the limitations of conventional chemotherapy (severe side effects and inefficacy due to the occurrence of multi-drug resistance). This review offers a comprehensive perspective of the first blockbuster chemotherapeutic agents of natural origin's (e.g. taxol, vincristine, doxorubicin) mechanism of action using 3D representation. In addition is portrayed the step-by-step evolution from preclinical to clinical evaluation of the most recently studied natural compounds with potent antitumor activity (e.g. resveratrol, curcumin, betulinic acid, etc.) in terms of anticancer mechanisms of action and the possible indications as chemotherapeutic or chemopreventive agents and sensitizers. Finally, this review describes several efficient platforms for the encapsulation and targeted delivery of natural compounds in cancer treatment.

Proniosomal Gel for Topical Delivery of Rutin: Preparation, Physicochemical Characterization and In Vitro Toxicological Profile Using 3D Reconstructed Human Epidermis Tissue and 2D Cells.

Rutin (Rut) is a natural flavonol, well-known for its broad-spectrum of therapeutic effects, including antioxidant and antitumoral activities; still, it has a reduced clinical outcome due to its limited solubility in aqueous solutions. To overcome this drawback, this study proposes a novel formulation for rutin as a proniosomal gel for cutaneous applications. The gel was prepared by coacervation phase-separation method and complies with the standard requirements in terms of particle size (140.5 ± 2.56 nm), zeta potential (-27.33 ± 0.09 mV), encapsulation capacity (> 50%), pH (7.002 ± 0.18) and rheological properties. The results showed high biocompatibility of the gel on the 3D reconstructed human epidermis model characterized by increased viability of the cells and a lack of irritant and phototoxic potential. The evaluations on 2D cells confirm the preferential cytotoxic effect of Rut on melanoma cells (IC50 value = 8.601 µM, nuclear fragmentation) compared to normal keratinocytes. Our data suggest that the proniosomal gel is a promising drug carrier for Rut in the management and prevention of skin disorders.

Silver Nanocolloids Loaded with Betulinic Acid with Enhanced Antitumor Potential: Physicochemical Characterization and In Vitro Evaluation.

Betulinic acid (BA), a natural compound with various health benefits including selective antitumor activity, has a limited applicability in vivo due to its poor water solubility and bioavailability. Thus, this study focused on obtaining a BA nano-sized formulation with improved solubility and enhanced antitumor activity using silver nanocolloids (SilCo and PEG_SilCo) as drug carriers. The synthesis was performed using a chemical method and the physicochemical characterization was achieved applying UV-Vis absorption, transmission electron microscopy (TEM), Raman and photon correlation spectroscopy (PCS). The biological evaluation was conducted on two in vitro experimental models-hepatocellular carcinoma (HepG2) and lung cancer (A549) cell lines. The physicochemical characterization showed the following results: an average hydrodynamic diameter of 32 nm for SilCo_BA and 71 nm for PEG_SilCo_BA, a spherical shape, and a loading capacity of 54.1% for SilCo_BA and 61.9% for PEG_SilCo_BA, respectively. The in vitro assessment revealed a cell type- and time-dependent cytotoxic effect characterized by a decrease in cell viability as follows: (i) SilCo_BA (66.44%) < PEG_SilCo_BA (72.05%) < BA_DMSO (75.30%) in HepG2 cells, and (ii) SilCo_BA (75.28%) < PEG_SilCo_BA (86.80%) < BA_DMSO (87.99%) in A549 cells. The novel silver nanocolloids loaded with BA induced an augmented anticancer effect as compared to BA alone.

Botanical Therapeutics (Part II): Antimicrobial and In Vitro Anticancer Activity against MCF7 Human Breast Cancer Cells of Chamomile, Parsley and Celery Alcoholic Extracts.

BACKGROUND: This study was designed as a continuation of a complex investigation about the phytochemical composition and biological activity of chamomile, parsley, and celery extracts against A375 human melanoma and dendritic cells. OBJECTIVE: The main aim was the evaluation of the antimicrobial potential of selected extracts as well as the in vitro anticancer activity against MCF7 human breast cancer cells. METHODS: In order to complete the picture regarding the phytochemical composition, molecular fingerprint was sketched out by the help of FTIR spectroscopy. The activity of two enzymes (acetylcholinesterase and butyrylcholinesterase) after incubation with the three extracts was spectrophotometrically assessed. The antimicrobial potential was evaluated by disk diffusion method. The in vitro anticancer potential against MCF7 human breast cancer cells was appraised by MTT, LDH, wound healing, cell cycle, DAPI, Annexin-V-PI assays. RESULTS: The results showed variations between the investigated extracts in terms of inhibitory activity against enzymes, such as acetyl- and butyrilcholinesterase. Chamomile and parsley extracts were active only against tested Gram-positive cocci, while all tested extracts displayed antifungal effects. Among the screened samples at the highest tested concentration, namely 60µg/mL, parsley was the most active extract in terms of reducing the viability of MCF7 - human breast adenocarcinoma cell line and inducing the release of lactate dehydrogenase. On the other hand, chamomile and celery extracts manifested potent anti-migratory effects. Furthermore, celery extract was the most active in terms of total apoptotic events, while chamomile extract induced the highest necrosis rate. CONCLUSION: The screened samples containing phytochemicals belonging in majority to the class of flavonoids and polyphenols can represent candidates for antimicrobial and anticancer agents.

Tetracyclic and Pentacyclic Triterpenes with High Therapeutic Efficiency in Wound Healing Approaches.

Wounds are among the most common skin conditions, displaying a large etiological diversity and being characterized by different degrees of severity. Wound healing is a complex process that involves multiple steps such as inflammation, proliferation and maturation and ends with scar formation. Since ancient times, a widely used option for treating skin wounds are plant- based treatments which currently have become the subject of modern pharmaceutical formulations. Triterpenes with tetracyclic and pentacyclic structure are extensively studied for their implication in wound healing as well as to determine their molecular mechanisms of action. The current review aims to summarize the main results of in vitro, in vivo and clinical studies conducted on lupane, ursane, oleanane, dammarane, lanostane and cycloartane type triterpenes as potential wound healing treatments.