Physalin D attenuates hepatic stellate cell activation and liver fibrosis by blocking TGF-β/Smad and YAP signaling.

Advances in the treatment of Chagas disease: Promising new drugs, plants and targets.

Objectives Withanolides are a group of modified C28 ergostane-type steroids with a C-22, C-26 δ-lactone side chain or a C-23, C-26 γ-lactone side chain. They enjoy a limited distribution in the plant kingdom and predominantly occur in several genera of Solanaceae. Of which, the genus Physalis is an important resource for this type of natural molecules. The present review aims to comprehensively illustrate the structural characteristics and classification of withanolides, and particularly focus on the progression on phytochemical and pharmacological aspects of withanolides from Physalis ranging from January 2015 to June 2019. Key findings Approximately 351 natural withanolides with novel and unique structures have so far been identified from genus Physalis, mainly isolated from the species of P. angulata and P. peruviana. Withanolides demonstrated diverse biological activity, such as anticancer, anti-inflammatory, antimicrobial, immunoregulatory, trypanocidal and leishmanicidal activity. Their observed pharmacological functions supported the uses of Physalis species in traditional or folk medicines. Summary Due to their unique structure skeleton and potent bioactivities, withanolides are regarded to be promising drug candidates, particularly for developing anticancer and anti-inflammatory agents. Further investigations for discovering novel withanolides of genus Physalis, exploiting their pharmacological values and evaluating their potency as therapeutic agents are significant work.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jphp.13209

Withanolides from the genus Physalis: a review on their phytochemical and pharmacological aspects.

Gomesin, a disulfide-rich antimicrobial peptide produced by the Brazilian spider Acanthoscurria gomesiana, has been shown to be potent against Gram-negative bacteria and to possess selective anticancer properties against melanoma cells. In a recent study, a backbone cyclized analogue of gomesin was shown to be as active but more stable than its native form. In the current study, we were interested in improving the antimicrobial properties of the cyclic gomesin, understanding its selectivity toward melanoma cells and elucidating its antimicrobial and anticancer mode of action. Rationally designed analogues of cyclic gomesin were examined for their antimicrobial potency, selectivity toward cancer cells, membrane-binding affinity, and ability to disrupt cell and model membranes. We improved the activity of cyclic gomesin by ∼10-fold against tested Gram-negative and Gram-positive bacteria without increasing toxicity to human red blood cells. In addition, we showed that gomesin and its analogues are more toxic toward melanoma and leukemia cells than toward red blood cells and act by selectively targeting and disrupting cancer cell membranes. Preference toward some cancer types is likely dependent on their different cell membrane properties. Our findings highlight the potential of peptides as antimicrobial and anticancer leads and the importance of selectively targeting cancer cell membranes for drug development.

Redesigned Spider Peptide with Improved Antimicrobial and Anticancer Properties.

Aberrant activation of Wnt/β-catenin signalling is critical in the progression of human cancers, especially colorectal cancer (CRC). Therefore, inhibition of Wnt/β-catenin signalling is a significant potential target for CRC therapy. Here, we identified for the first time that Physalin F (PF), a steroid derivative isolated from Physalis angulate, acts as an antagonist of Wnt/β-catenin signalling. In vitro, PF decreased Wnt3a-induced TOPFlash reporter activity in HEK293T cells and promoted the formation of the β-catenin destruction complex. Importantly, PF also inhibited Wnt/β-catenin signalling and accelerated the degradation of β-catenin in CRC cells. However, PF did not affect the stabilization of Axin or the interaction of β-catenin with E-cadherin. Interestingly, we further found that PF promoted YAP binding to the β-catenin destruction complex, which facilitated the ubiquitination and degradation of β-catenin. Silencing and pharmacological inhibition of YAP reversed the formation of the β-catenin destruction complex induced by PF, implying that YAP binding to the β-catenin destruction complex was responsible for PF-mediated inhibition of Wnt/β-catenin signalling. Furthermore, PF observably inhibited tumour growth by down-regulating β-catenin in tumour-bearing mice. Collectively, our findings indicated that PF inhibited Wnt/β-catenin signalling by accelerating the ubiquitination and degradation of β-catenin in a YAP-dependent manner and therefore PF could be a novel potential candidate for CRC therapy.

/pdf/yap-dependent-ubiquitination-and-degradation-of-b-catenin-22fg4wtv5c.pdf

YAP-dependent ubiquitination and degradation of β-catenin mediates inhibition of Wnt signalling induced by Physalin F in colorectal cancer

https://www.arca.fiocruz.br/bitstream/icict/13713/2/Meira%2c%20CS%20In%20vitro%20and%20.....pdf

In vitro and in vivo antiparasitic activity of Physalis angulata L. concentrated ethanolic extract against Trypanosoma cruzi.

https://www.arca.fiocruz.br/bitstream/icict/14265/2/Pinto%20LA%20Physalin%20F%20a%20seco-steroid%20from%20Physalis....pdf

Physalin F, a seco-steroid from Physalis angulata L., has immunosuppressive activity in peripheral blood mononuclear cells from patients with HTLV1-associated myelopathy.

This paper intends to reveal the innovation in knowledge production in Infectious Diseases field, particularly in the branch of Health Promotion research of Epidemiology and Social Health Determination Research Laboratory. This branch combines projects which aim to build new ways of promoting health and forms of knowledge production, through workshops, lectures, visits to scientific exhibitions, science centers, museums, and sociocultural activities requested by patients, their families/friends and collaborators of Evandro Chagas National Institute of Infectious Diseases (INI). The activities include a partnership with “Association "Fighting to Live - Friends of INI”, an organization led by volunteers and patients. One of the suggestions of the participants was to hold workshops on Brazilian literature and storytelling history of diseases. We seek to share knowledge on leishmaniasis and tuberculosis, frequent diseases in the INI, and we also invite them to participate in some ludic activities. We approach the history of these diseases, transmission, epidemiology, prevention, treatment and control. We conducted two workshops at different times: the "Cordel Literature in Health and Science", using the booklet "The Be-A-Ba of leishmaniasis" and "Noel Rosa: Music, Art and Tuberculosis". This innovative action has contributed to the production and expansion of knowledge, a way of improving the quality of life, self-esteem enhancement, and social inclusion of citizens.

/pdf/inovacoes-na-producao-do-conhecimento-em-doencas-infeciosas-5db1yxyacg.pdf

Inovações na produção do conhecimento em doenças infeciosas: história, arte, cultura e epidemiologia

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In vitro and in vivo antiparasitic activity of Physalis angulata L. concentrated ethanolic extract against Trypanosoma cruzi.

Physalin F, a seco-steroid from Physalis angulata L., has immunosuppressive activity in peripheral blood mononuclear cells from patients with HTLV1-associated myelopathy.

Inovações na produção do conhecimento em doenças infeciosas: história, arte, cultura e epidemiologia