Since chronic inflammation can be seen in severe, long-lasting diseases such as cancer, there is a high demand for effective methods to modulate inflammatory responses. Among many therapeutic candidates, lignans, absorbed from various plant sources, represent a type of phytoestrogen classified into secoisolariciresionol (Seco), pinoresinol (Pino), matairesinol (Mat), medioresinol (Med), sesamin (Ses), syringaresinol (Syr), and lariciresinol (Lari). Lignans consumed by humans can be further modified into END or ENL by the activities of gut microbiota. Lignans are known to exert antioxidant and anti-inflammatory activities, together with activity in estrogen receptor-dependent pathways. Lignans may have therapeutic potential for postmenopausal symptoms, including cardiovascular disease, osteoporosis, and psychological disorders. Moreover, the antitumor efficacy of lignans has been demonstrated in various cancer cell lines, including hormone-dependent breast cancer and prostate cancer, as well as colorectal cancer. Interestingly, the molecular mechanisms of lignans in these diseases involve the inhibition of inflammatory signals, including the nuclear factor (NF)-κB pathway. Therefore, we summarize the recent in vitro and in vivo studies evaluating the biological effects of various lignans, focusing on their values as effective anti-inflammatory agents.

Nuclear factor kappa B (NF-κB) signaling pathways progress inflammation and immune cell differentiation in the host immune response; however, the uncontrollable stimulation of NF-κB signaling is responsible for several inflammatory illnesses regardless of whether the conditions are acute or chronic. Innate immune cells, such as macrophages, microglia, and Kupffer cells, secrete pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β, via the activation of NF-κB subunits, which may lead to the damage of normal cells, including neurons, cardiomyocytes, hepatocytes, and alveolar cells. This results in the occurrence of neurodegenerative disorders, cardiac infarction, or liver injury, which may eventually lead to systemic inflammation or cancer. Recently, ginsenosides from Panax ginseng, a historical herbal plant used in East Asia, have been used as possible options for curing inflammatory diseases. All of the ginsenosides tested target different steps of the NF-κB signaling pathway, ameliorating the symptoms of severe illnesses. Moreover, ginsenosides inhibit the NF-κB-mediated activation of cancer metastasis and immune resistance, significantly attenuating the expression of MMPs, Snail, Slug, TWIST1, and PD-L1. This review introduces current studies on the therapeutic efficacy of ginsenosides in alleviating NF-κB responses and emphasizes the critical role of ginsenosides in severe inflammatory diseases as well as cancers.

Linosorbs (Los) are cyclic peptides from flaxseed oil composed of the LO mixture (LOMIX). The activity of LO has been reported as being anti-cancer and anti-inflammatory. However, the study of skin protection has still not proceeded. In particular, there are poorly understood mechanisms of melanogenesis to LO. Therefore, we investigated the anti-melanogenesis effects of LOMIX and LO, and its activity was examined in mouse melanoma cell lines. The treatment of LOMIX (50 and 100 μg/mL) and LO (6.25–50 μM) suppressed melanin secretion and synthesis, which were 3-fold increased, in a dose-dependent manner, up to 95%. In particular, [1–9-NαC]-linusorb B3 (LO1) and [1-9-NαC]-linusorb B2 (LO2) treatment (12.5 and 25 μM) highly suppressed the synthesis of melanin in B16F10 cell lines up to 90%, without toxicity. LOMIX and LOs decreased the 2- or 3-fold increased mRNA levels, including the microphthalmia-associated transcription factor (MITF), Tyrosinase, tyrosinase-related protein 1 (TYRP1), and tyrosinase-related protein 2 (TYRP2) at the highest concentration (25 μM). Moreover, the treatment of 25 μM LO1 and LO2 inhibited the expression of MITF and phosphorylation of upper regulatory proteins such as CREB and PKA. Taken together, these results suggested that LOMIX and its individual LO could inhibit melanin synthesis via downregulating the CREB-dependent signaling pathways, and it could be used for novel therapeutic materials in hyperpigmentation.

Growing demand for treatment options against acute lung injury (ALI) emphasizes studies on plant extracts harboring anti-inflammatory effects. According to GC-MS analysis, Angiopteris cochinchinensis de Vriese consists of various flavonoids with anti-inflammatory activities. Thus, in this study, the anti-inflammatory effects of an extract of Angiopteris cochinchinensis de Vriese (Ac-EE) were assessed using RAW264.6 murine macrophages and a lipopolysaccharide (LPS)-induced ALI model. Ac-EE reduced the nitric oxide production in murine macrophages increased by LPS induction. Moreover, protective effects of Ac-EE on lung tissue were demonstrated by shrinkage of edema and lung injury. Reduced neutrophil infiltration and formation of hyaline membranes were also detected in lung tissues after H&E staining. Semiquantitative RT-PCR, quantitative real-time PCR, and ELISA showed that Ac-EE inhibits the production of proinflammatory mediators, including iNOS and COX-2, and cytokines, such as TNF-α, IL-1β, and IL-6. An Ac-EE-mediated anti-inflammatory response was derived from inhibiting the NF-κB signaling pathway, which was evaluated by luciferase reporter assay and Western blotting analysis. A cellular thermal shift assay revealed that the prime target of Ac-EE in alleviating inflammation was Src. With its direct binding with Src, Angiopteris cochinchinensis de Vriese significantly mitigates lung injury, showing possibilities of its potential as an effective botanical drug.

There is a growing demand for hair loss treatments with minimal side effects and recurrence potential. Connarus semidecandrus Jack has been used as a folk medicine for fever in tropical regions, but its anti-alopecia effects remain unclear. In this study, the anti-androgenic alopecia effect of an ethanol extract of Connarus semidecandrus Jack (Cs-EE) was demonstrated in a testosterone-induced androgenic alopecia (AGA) model, in terms of the hair–skin ratio, hair type frequency, and hair thickness. The area of restored hair growth and thickened hair population after Cs-EE treatment showed the hair-growth-promoting effect of Cs-EE. Histological data support the possibility that Cs-EE could reduce hair loss and upregulate hair proliferation in mouse skin by shifting hair follicles from the catagen phase to the anagen phase. Western blotting indicated that Cs-EE reduced the expression of the androgenic receptor. Cs-EE treatment also inhibited programmed cell death by upregulating Bcl-2 expression at the mRNA and protein levels. The anti-alopecia effect of Cs-EE was confirmed by in vitro experiments showing that Cs-EE had suppressive effects on 5-α reductase activity and lymph node carcinoma of the prostate proliferation, and a proliferative effect on human hair-follicle dermal papilla (HDP) cells. Apoptotic pathways in HDP cells were downregulated by Cs-EE treatment. Thus, Cs-EE could be a potential treatment for AGA.

Colorectal cancer (CRC) poses a significant health burden worldwide and necessitates novel treatment approaches with fewer side effects than conventional chemotherapy. Many natural compounds have been tested as possible cancer treatments. Plants in the genus Panax have been widely studied due to their therapeutic potential for various diseases such as inflammatory disorders and cancers. Extracts from plants of genus Panax activate upstream signals, including those related to autophagy and the generation of reactive oxygen species, to induce intrinsic apoptosis in CRC cells. The root extract of Panax notoginseng (P. notoginseng) regulated the gut microbiota to enhance the T-cell-induced immune response against CRC. Protopanaxadiol (PPD)-type ginsenosides, especially Rh2, Rg3, Rb1, and Rb2, significantly reduced proliferation of CRC cells and tumor size in a xenograft mouse model, as well as targeting programmed death (PD)-1 to block the immune checkpoint of CRC cells. Moreover, modified nanocarriers with ginsenosides upregulated drug efficacy, showing that ginsenosides can also be utilized as drug carriers. An increasing body of studies has demonstrated the potential of the genus Panax in curing CRC. Ginsenosides are promising active compounds in the genus Panax, which can also support the activity of conventional cancer therapies.