Natural products obtained in dietary components may aid the prevention and treatment of a variety of diseases. Reports in the scientific literature have demonstrated that the consumption of terpenes is a successful alternative in the treatment of several diseases, triggering beneficial biological effects in clinical and preclinical studies. The monoterpene limonene is largely used in alimentary items, cleaning products, and it is one of the most frequent fragrances used in cosmetics formulation. The therapeutic effects of limonene have been extensively studied, proving anti-inflammatory, antioxidant, antinociceptive, anticancer, antidiabetic, antihyperalgesic, antiviral, and gastroprotective effects, among other beneficial effects in health. In this review, we collected, presented, and analyzed evidence from the scientific literature regarding the usage of limonene and its activities and underlying mechanisms involved in combating diseases. The highlighting of limonene applications could develop a useful targeting of innovative research in this field as well as the development of a limonene-based phytomedicine which could be used in a variety of conditions of health and disease.

Este estudo objetivou caracterizar qualitativamente grupos de metabólitos secundários e alguns constituintes de 9 espécies de plantas medicinais nativas do cerrado utilizadas pela comunidade rural do Assentamento Vale Verde, identificando potencialidades biológicas e farmacológicas. As informações referentes às plantas de uso medicinal foram obtidas por meio de estudos etnobotânicos e etnofarmacológicos, realizados no período de 2010 a 2012. O material botânico coletado foi identificado e depositado no Herbário da Universidade Federal do Tocantins, Porto Nacional (TO). O extrato etanólico e metanólico foi obtido a partir do material seco em estufa, filtrado e concentrado em evaporador rotatório sob pressão reduzida, pesados e novamente colocados em estufa por 24h a 50ºC, obtendo o rendimento (m/m) resultante da relação entre a massa de extrato concentrado e após seco. A análise fitoquímica das plantas selecionadas foi feita usando a metodologia da Prospecção Preliminar, realizando testes para detecção de alguns constituintes importantes e dos principais grupos de metabólitos: saponinas, fenóis e taninos, catequinas, esteróides e triterpenóides, cumarinas, antraquinonas e flavonóides. Os testes foram considerados positivos através de reações de precipitados com colorações, formações de espumas e manchas coloridas. Os testes fitoquímicos realizados nos extratos revelarem a presença de constituintes do metabolismo secundário das plantas que podem contribuir para a identificação de marcadores químicos para as espécies estudadas, sendo estes indispensáveis para os testes de qualidade e integridade de fitoterápicos e uso popular mais seguro das plantas medicinais, possibilitando melhor controle farmacognóstico dessas espécies e direcionamento dos seus usos e aplicações na pesquisa pela bioatividade preliminarmente conhecida. Neste caso, especialmente devido às atividades antimicrobianas, antioxidantes e contra insetos, sugerindo relação com a presença de compostos fenólicos e flavonoídicos, positivos nos extratos da maioria das espécies. Estas informações são inéditas no Tocantins e estratégicas para fortalecimento das políticas de conservação de Áreas de Reserva Legal no âmbito do Cerrado, bioma prioritário para conservação da biodiversidade, melhorando a caracterização dos recursos medicinais ainda disponíveis na flora nativa regional bem como vislumbrando suas aplicações biológicas e farmacológicas.

The skin is the biggest organ of human body which acts as a protective barrier against deleterious agents. When this barrier is damaged, the organism promotes the healing process with several molecular and cellular mechanisms, in order to restore the physiological structure of the skin. The physiological control of wound healing depends on the correct balance among its different mechanisms. Any disruption in the balance of these mechanisms can lead to problems and delay in wound healing. The impairment of wound healing is linked to underlying factors as well as aging, nutrition, hypoxia, stress, infections, drugs, genetics, and chronic diseases. Over the years, numerous studies have been conducted to discover the correct approach and best therapies for wound healing, including surgical procedures and non-surgical treatments such as topical formulations, dressings, or skin substitutes. Thus, this general approach is necessary to facilitate the direction of further studies. This work provides updated concepts of physiological mechanisms, the factors that can interfere, and updated treatments used in skin wound healing.

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The wound healing is a complex process which, sometimes, can be a problem in public health because of the possibility of physical disability or even death. Due to the lack of a gold standard drug in skin wound treatment and aiming at the discovery of new treatments in skin repair and the mechanisms involved in the process, we used oleoresin (OR) from Copaifera langsdorffii and hydroalcoholic extract of the leaves (EH) to treat rat skin wounds. For that, male Wistar rats were divided into groups ( = 8): Lanette, Collagenase, 10% EH, or 10% OR and, after anesthesia, one wound of 2 cm was made in the back of animals. The wounds were treated once a day for 3, 7, or 14 days and the wound areas were measured. The rats were euthanized and skin samples destined to biochemical, molecular, and immunohistochemical analysis. The results showed a macroscopic retraction of the wounds of 10% EH and 10% OR creams and both treatments showed anti-inflammatory activity. Molecular and immunohistochemical results demonstrated the activity of Copaifera langsdorffii creams in angiogenesis, reepithelialization, wound retraction, and remodeling mechanisms.

Skin wound healing is a dynamic and complex process involving several mediators at the cellular and molecular levels. Lupeol, a phytoconstituent belonging to the triterpenes class, is found in several fruit plants and medicinal plants that have been the object of study in the treatment of various diseases, including skin wounds. Various medicinal properties of lupeol have been reported in the literature, including anti-inflammatory, antioxidant, anti-diabetic, and anti-mutagenic effects. We investigated the effects of lupeol (0.1, 1, 10, and 20 μg/mL) on in vitro wound healing assays and signaling mechanisms in human neonatal foreskin keratinocytes and fibroblasts. Results showed that, at high concentrations, Lupeol reduced cell proliferation of both keratinocytes and fibroblasts, but increased in vitro wound healing in keratinocytes and promoted the contraction of dermal fibroblasts in the collagen gel matrix. This triterpene positively regulated matrix metalloproteinase (MMP)-2 and inhibited the NF-κB expression in keratinocytes, suggesting an anti-inflammatory effect. Lupeol also modulated the expression of keratin 16 according to the concentration tested. Additionally, in keratinocytes, lupeol treatment resulted in the activation of Akt, p38, and Tie-2, which are signaling proteins involved in cell proliferation and migration, angiogenesis, and tissue repair. These findings suggest that lupeol has therapeutic potential for accelerating wound healing.

Impaired wound healing is a debilitating complication of diabetes that leads to significant morbidity, particularly foot ulcers. Natural products have shown to be effective in treating skin wounds. Lupeol is known to stimulate angiogenesis, fibroblast proliferation, and expressions of cytokines and growth factors involved in wound healing. The study is performed to evaluate the wound healing activity of lupeol in streptozotocin-induced hyperglycemic rats by macroscopical, histological, immunohistochemical, immunoenzymatic, and molecular methods. Percentage of wound closure and contraction was increased in the lupeol-treated group when compared to the Lanette group. Histopathological observation revealed decreased inflammatory cell infiltration and increased proliferation of fibroblasts, vascularization, and deposition of collagen fibers after lupeol treatment. Immunohistochemical analyses showed decreased intensity of NF-κB and increased intensity of FGF-2, TGF-β1, and collagen III. ELISA results revealed downregulated IL-6 levels and upregulated IL-10 levels in response to lupeol. The mRNA expression levels of Hif-1α, Sod-2, and Ho-1 were significantly increased in response to lupeol as compared to Lanette whereas Nf-κb and Vegf-A levels were decreased in relation to insulin and lupeol treatment. These findings indicate that lupeol possesses wound healing potential in hyperglycemic conditions and may be useful as a treatment for chronic wounds in diabetic patients.

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