The secondary metabolites of clerodane diterpenoids have been found in several plant species from various families and in other organisms. In this review, we included articles on clerodanes and neo-clerodanes with cytotoxic or anti-inflammatory activity from 2015 to February 2023. A search was conducted in the following databases: PubMed, Google Scholar and Science Direct, using the keywords clerodanes or neo-clerodanes with cytotoxicity or anti-inflammatory activity. In this work, we present studies on these diterpenes with anti-inflammatory effects from 18 species belonging to 7 families and those with cytotoxic activity from 25 species belonging to 9 families. These plants are mostly from the Lamiaceae, Salicaceae, Menispermaceae and Euphorbiaceae families. In summary, clerodane diterpenes have activity against different cell cancer lines. Specific antiproliferative mechanisms related to the wide range of clerodanes known today have been described, since many of these compounds have been identified, some of which we barely know their properties. It is very possible that there are even more compounds than those described today, in such a way that makes it an open field to discover. Furthermore, some diterpenes presented in this review have already-known therapeutic targets, and therefore, their potential adverse effects can be predicted in some way.

Systemic sclerosis (SSc) is an autoimmune disease with three pathogenic hallmarks, i.e., inflammation, vasculopathy, and fibrosis. A wide plethora of animal models have been developed to address the complex pathophysiology and for the development of possible anti-fibrotic treatments. However, no current model comprises all three pathological mechanisms of the disease. To highlight the lack of a complete model, a review of some of the most widely used animal models for SSc was performed. In addition, to date, no model has accomplished the recreation of primary or secondary Raynaud’s phenomenon, a key feature in SSc. In humans, nailfold capillaroscopy (NFC) has been used to evaluate secondary Raynaud’s phenomenon and microvasculature changes in SSc. Being a non-invasive technique, it is widely used both in clinical studies and as a tool for clinical evaluation. Because of this, its potential use in animal models has been neglected. We evaluated NFC in guinea pigs to investigate the possibility of applying this technique to study microcirculation in the nailfold of animal models and in the future, development of an animal model for Raynaud’s phenomenon. The applications are not only to elucidate the pathophysiological mechanisms of vasculopathy but can also be used in the development of novel treatment options.

Introdução: A depressão representa um grave problema de saúde pública, modificando significativamente a qualidade de vida dos pacientes. Sem um mecanismo biológico completamente estabelecido que desencadeie seus sintomas característicos, envolve diversos fatores etiológicos, como a modificação da microbiota intestinal, a qual participa da comunicação bidirecional do eixo intestino-cérebro. Devido à disbiose, alterações na comunicação desse eixo podem ter uma correlação direta com patologias mentais, como a depressão. Objetivos: Realizou-se uma revisão bibliográfica para revisitar os principais mecanismos que correlacionam a microbiota intestinal com a patogênese da depressão e a relação da sua modulação como uma opção terapêutica para essa patologia. Metodologia: A pesquisa incluiu dados de 35 artigos científicos publicados entre 2002 e 2018 nas bases de dados do Pubmed e Scielo, acerca do tema proposto. Resultados: A microbiota intestinal é importante para a função do SNC, devido à comunicação bidirecional intestino-cérebro, permitindo que este influencie nas funções gastrintestinais e imunológicas. Como a microbiota regula o epitélio intestinal, fatores emocionais podem interferir na composição da mesma e na integridade dos enterócitos. A disbiose interfere na produção de citocinas e altera a permeabilidade intestinal - quando acentuada, produtos bacterianos desencadeiam um quadro inflamatório, evidenciado em pacientes com depressão. Estes também podem apresentar diferenças na composição da microbiota e seu tratamento com probióticos específicos podem reduzir sintomas depressivos. Conclusão: Apesar dos escassos estudos em humanos, há intensa inter-relação entre microbiota, eixo intestino-cérebro e patologias mentais. Portanto, a modulação da microbiota cria uma nova perspectiva acerca da fisiopatogenia, prevenção e tratamento da depressão.

The role of leukotrienes (LTs) in the pathogenesis of systemic sclerosis (SSc) needs clarification. We analyzed the association of salivary (sa) and plasma (p) levels (pg/mL) of cysteinyl-leukotrienes (CysLT) and LTB4 with SSc vascular manifestations and nailfold capillaroscopy (NFC) in a cross-sectional study. Patients and healthy controls were evaluated for vascular manifestations and NFC. LTs were compared between groups as follows: SSc with or SSc without vascular features and controls, and by NFC parameters. Twenty SSc patients and 16 volunteers were recruited; Raynaud’s phenomenon (RP) history (SSc: saCysLT 99.4 ± 21.8 vs. controls: 23.05 ± 23.7, p = 0.01), RP at examination (SSc: saCysLT 129.3 ± 24.6 vs. controls: 23.05 ± 22.46, p = 0.01; pCysLT SSc: 87.5 ± 11.2 vs. controls: 32.37 ± 10.75, p = 0.002), capillary loss (saCysLT 138.6 ± 26.7 vs. 23.05 ± 21.6, p = 0.0007; saLTB4 3380.9 ± 426.6 vs. 1216.33 ± 346.1, p = 0.0005), “late” scleroderma pattern vs. controls (saCysLT 205.6 ± 32 vs. 23 ± 19.6, p = 0.0002; saLTB4 4564.9 ± 503.6 vs. 1216.3 ± 308.3; p < 0.0001) were all significant. Late patterns had higher levels (saCysLT, p = 0.002; LTB4 p = 0.0006) compared to active and early patterns (LTB4, p = 0.0006), and giant capillaries (p = 0.01) showed higher levels of LTs. Levels of pCysLT were higher in patients with RP at examination vs. patients without RP; saCysLT and LTB4 were higher in SSc group with vs. without capillary loss. LTs could be involved in the pathophysiology of vascular abnormalities. Further research is required to determine if blocking LTs could be a therapeutic target for SSc vascular manifestations.

We report the case of an 87‐year‐old woman whose initial presentation was palpable purpura. Henoch–Schönlein purpura was initially diagnosed, for which she received intravenous methylprednisolone and epinastine, resulting in complete remission of the skin lesions. After discontinuation of corticosteroid therapy, she experienced multiple relapses over the ensuing months with an incomplete response to medical treatment. Metastatic breast cancer was diagnosed 7 months later, which retrospectively suggested a paraneoplastic etiology for the vasculitis. Although the association between cutaneous vasculitis and malignancy—particularly hematologic cancers—is well documented, the underlying mechanisms remain poorly understood. The link with breast cancer is rare, though sporadically reported. Vasculitis in this context may occur before, during, or after cancer diagnosis or treatment. Notably, only two cases of breast cancer–associated vasculitis have been reported in patients aged 80 or older. Paraneoplastic vasculitis typically resolves with treatment of the underlying malignancy. However, given the presence of metastatic disease in this patient, immunosuppressive therapy with azathioprine was needed, resulting in complete resolution of lesions.