Dioscorea spp. belongs to the Dioscoreaceae family, known as “yams”, and contains approximately 600 species with a wide distribution. It is a major food source for millions of people in tropical and subtropical regions. Dioscorea has great medicinal and therapeutic capabilities and is a potential source of bioactive substances for the prevention and treatment of many diseases. In recent years, increasing attention has been paid to the phytochemicals of Dioscorea, such as steroidal saponins, polyphenols, allantoin, and, in particular, polysaccharides and diosgenin. These bioactive compounds possess anti-inflammatory activity and are protective against a variety of inflammatory diseases, such as enteritis, arthritis, dermatitis, acute pancreatitis, and neuroinflammation. In addition, they play an important role in the prevention and treatment of metabolic diseases, including obesity, dyslipidemia, diabetes, and non-alcoholic fatty liver disease. Their mechanisms of action are related to the modulation of a number of key signaling pathways and molecular targets. This review mainly summarizes recent studies on the bioactive compounds of Dioscorea and its treatment of inflammatory and metabolic diseases, and highlights the underlying molecular mechanisms. In conclusion, Dioscorea is a promising source of bioactive components and has the potential to develop novel natural bioactive compounds for the prevention and treatment of inflammatory and metabolic diseases.

Cx43 hemichannels (HCs) and Panx1 channels are two genetically distant protein families. Despite the lack of sequence homology, Cx43 and Panx1 channels have been the subject of debate due to their overlapping expression and the fact that both channels present similarities in terms of their membrane topology and electrical properties. Using the mimetic peptides Gap19 and ¹⁰Panx1, this study aimed to investigate the cross-effects of these peptides on Cx43 HCs and Panx1 channels. The single-channel current activity from stably expressing HeLa-Cx43 and C6-Panx1 cells was recorded using patch-clamp experiments in whole-cell voltage-clamp mode, demonstrating 214 pS and 68 pS average unitary conductances for the respective channels. Gap19 was applied intracellularly while ¹⁰Panx1 was applied extracellularly at different concentrations (100, 200 and 500 μM) and the average nominal open probability (NP_o) was determined for each testing condition. A concentration of 100 µM Gap19 more than halved the NP_o of Cx43 HCs, while 200 µM ¹⁰Panx1 was necessary to obtain a half-maximal NP_o reduction in the Panx1 channels. Gap19 started to significantly inhibit the Panx1 channels at 500 µM, reducing the NP_o by 26% while reducing the NP_o of the Cx43 HCs by 84%. In contrast ¹⁰Panx1 significantly reduced the NP_o of the Cx43 HCs by 37% at 100 µM and by 83% at 200 µM, a concentration that caused the half-maximal inhibition of the Panx1 channels. These results demonstrate that ¹⁰Panx1 inhibits Cx43 HCs over the 100–500 µM concentration range while 500 µM intracellular Gap19 is necessary to observe some inhibition of Panx1 channels.

Inositol 1,4,5-trisphosphate (IP₃) receptor channels are intracellular ion channels activated by IP₃ and provoking Ca²⁺ release from ER/SR stores, playing fundamental roles in various cell functions ranging from fertilization up to cell death control. The channels are tetrameric structures centered around a Ca²⁺-permeable pore, which mutually interact to control channel opening initiated by both IP₃ and cytoplasmic Ca²⁺. IP₃ receptor (IP3R) channels come in 3 distinct subtypes with cryo-EM data currently being available for IP3R1 and IP3R3. These studies have demonstrated that IP₃ association with the IP₃ binding core (IBC) of a given subunit, triggers retraction of the ARM2 domain in a neighbor subunit, leading to IP₃ capture by the IBC of the initiating subunit, demonstrating subunit collaboration. ARM2 of IP3R2/3 contains a self-binding peptide that associates with the IBC but becomes displaced upon ARM2 retraction, thereby uncovering the IBC of a neighbor subunit, facilitating IP₃ access and thus potentially providing subunit cooperation. Distinct from collaboration, subunit cooperation has the potential to be forwarded across all 4 subunits. We here provide novel insight and understanding on the role of both IP₃ and Ca²⁺ in the steeply negative Hill behavior observed for IP3R inhibition by IP3RPEP6, a self-binding peptide derived from the ARM2 domain. In this light, we discuss the broad variety of reported IP3R Hill slopes and conclude that subunit cooperation operates at both activation and inhibition levels, suggesting adaptability to the cell state to either provide a well-titrated or an all-or-nothing response depending on the conditions and necessity.