Systemic sclerosis (SSc) is a rare multisystemic autoimmune disease associated with progressive fibrosis, vasculopathy, and immune dysregulation. Despite advances in its management, the disease remains associated with substantial morbidity and mortality, with limited therapeutic options. This systematic review aimed to identify phytocompounds and medicinal plants that had demonstrated efficacy in SSc. A comprehensive literature search was performed in PubMed and ScienceDirect, yielding 7797 records, of which 32 studies met the inclusion criteria. A second search was performed using the SwissTargetPrediction tool to identify new putative molecular targets for these phytocompounds, whose relevance for SSc pathogenesis was verified by a third search in PubMed and ScienceDirect databases. Our search found 24 phytocompouds (e.g., halofunginone, crocetin, and tanshinone IIA) and 5 plant extracts (e.g., caper bush and ciplukan) reported to modulate key pathogenic processes in SSc. These phytochemicals were mainly associated with effects on endothelial to mesenchymal transition, oxidative stress, inflammation, and profibrotic signaling pathways, particularly TGF-β/Smad. The SwissTargetPrediction tool indicated 93 new potential molecular targets of the selected phytochemicals, among which only 41 showed relevance to SSc pathogenesis. In conclusion, available evidence is scarce but promising. Further studies, especially human investigations, are required to clarify clinical efficacy, safety, and potential interactions with drugs used in SSc.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disorder characterized by complex interactions between the innate and adaptive immune systems, being potentially associated with an enhanced intestinal permeability. Zonulin represents a key protein in the modulation of intestinal permeability, being a gut leakage marker. The purpose of the present work was to evaluate the intestinal permeability, through serum zonulin levels, and to explore the relationships between zonulin, disease activity, and organ involvement in Caucasian SLE patients. The study had a cross-sectional design and included two groups of subjects: the SLE group (n = 41) and the control group (n = 29). Plasma zonulin level was measured using indirect ELISA. Despite the fact that Caucasian SLE patients exhibited higher plasma zonulin levels compared to the control group (7.566 ± 1.368 ng/mL vs. 2.306 ± 0.286 ng/mL, p < 0.01, Mann–Whitney-U-test), plasma zonulin levels did not correlate with disease activity measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). SLE patients with clinical articular involvement had paradoxically lower plasma zonulin levels than those without this manifestation. The results support the hypothesis of a mutually exclusive inflammatory “signature” between intestinal mucosa and synovium.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder with a chronic intermittent course, a characteristic that suggests an involvement of divergent channels. According to Chinese medicine, divergent channels divert the pathogens to joints, where they are held transiently in a latent state, in order to keep them away from internal organs. The purpose of the present work is to determine whether, in SLE subjects, the levels of certain markers of gut leakage (zonulin), fungal translocation or proliferation of [(1→3)-β-D-glucan], and protective mechanisms (FGF21) are associated with the type of organ involvement or with the type of joint involvement (small vs. large joints) and to explore potential connections with the Chinese medicine perspective on SLE, conceptualized as pathology of the divergent channels. Methods: The study had a cross-sectional design and included an SLE group (n = 33) and a control group (n = 24) of subjects. Plasma levels of zonulin, (1→3)-β-D-glucan, and FGF21 were measured using indirect ELISA. Results: Despite the fact that SLE patients exhibited higher plasma zonulin levels when compared to controls [4.709 (1.996–10.426), n = 33 vs. 1.973 (1.371–3.05925), n = 24, p = 0.004], [median (IQR)], there was no difference in plasma zonulin levels between SLE patients with large joint involvement and controls. Plasma (1→3)-β-D-glucan was also higher in the SLE group than in controls [119.444 (82.746–277.66), n = 33 vs. 77.893 (47.524–124.7495), n = 24, p = 0.01]. Cutaneous involvement was significantly more frequent in patients with large joint (p = 0.03) and small joint (p = 0.006) involvement than in those without articular involvement. Conclusions: Plasma zonulin may be correlated with the degree of SLE latency in joints (divergent channels activation). The engagement of divergent channels, reflected by articular involvement, appears to be associated with a greater propensity for sinew channel activation as a potential mechanism of pathogen evacuation.