Hederagenin (HG) is a natural pentacyclic triterpenoid that can be isolated from various medicinal herbs. By modifying the structure of HG, multiple derivatives with superior biological activities and safety profiles have been designed and synthesized. Accumulating evidence has demonstrated that HG and its derivatives display multiple pharmacological activities against cancers, inflammatory diseases, infectious diseases, metabolic diseases, fibrotic diseases, cerebrovascular and neurodegenerative diseases, and depression. Previous studies have confirmed that HG and its derivatives combat cancer by exerting cytotoxicity, inhibiting proliferation, inducing apoptosis, modulating autophagy, and reversing chemotherapy resistance in cancer cells, and the action targets involved mainly include STAT3, Aurora B, KIF7, PI3K/AKT, NF-κB, Nrf2/ARE, Drp1, and P-gp. In addition, HG and its derivatives antagonize inflammation through inhibiting the production and release of pro-inflammatory cytokines and inflammatory mediators by regulating inflammation-related pathways and targets, such as NF-κB, MAPK, JAK2/STAT3, Keap1-Nrf2/HO-1, and LncRNA A33/Axin2/β-catenin. Moreover, anti-pathogen, anti-metabolic disorder, anti-fibrosis, neuroprotection, and anti-depression mechanisms of HG and its derivatives have been partially elucidated. The diverse pharmacological properties of HG and its derivatives hold significant implications for future research and development of new drugs derived from HG, which can lead to improved effectiveness and safety profiles.

Metformin (Met), a first-line management for type 2 diabetes mellitus, has been expansively employed and studied with results indicating its therapeutic potential extending beyond glycemic control. Beyond its established role, this therapeutic drug demonstrates a broad spectrum of action encompassing over 60 disorders, encompassing metabolic conditions, inflammatory disorders, carcinomas, cardiovascular diseases, and cerebrovascular pathologies. There is clear evidence of Met\'s action targeting specific nodes in the molecular pathways of these diseases and, intriguingly, interactions with the intestinal microbiota and epigenetic processes have been explored. Furthermore, novel Met derivatives with structural modifications tailored to diverse diseases have been synthesized and assessed. This manuscript proffers a comprehensive thematic review of the diseases amenable to Met treatment, elucidates their molecular mechanisms, and employs informatics technology to prospect future therapeutic applications of Met. These data and insights gleaned considerably contribute to enriching our understanding and appreciation of Met\'s far-reaching clinical potential and therapeutic applicability.

Berberine (BBR) is a plant derived quaternary benzylisoquinoline alkaloid, which has been widely used in traditional medicines for a long term. It possesses broad pharmacological effects and is widely applied in clinical. In recent years, the anti-tumor effects of BBR have attracted more and more attention of the researchers. The canonical right-handed double-stranded helical deoxyribonucleic acid (B-DNA) and its polymorphs occur under various environmental conditions and are involved in a plethora of genetic instability-related diseases especially tumor. BBR showed differential binding effects towards various polymorphic DNA structures. But its poor lipophilicity and fast metabolism limited its clinical utility. Structural modification of BBR is an effective approach to improve its DNA binding activity and bioavailability in vivo. A large number of studies dedicated to improving the binding affinities of BBR towards different DNA structures have been carried out and achieved tremendous advancements. In this article, the main achievements of BBR derivatives in polymorphic DNA structures binding researches in recent 20 years were reviewed. The structural modification strategy of BBR, the DNA binding effects of its derivatives, and the structure activity relationship (SAR) analysis have also been discussed.

BACKGROUND: Baishouwu has been used in China for thousands of years since it was first discovered in the late Tang Dynasty and flourished in the Song and Ming Dynasties. The Chinese herbal medicines named Baishouwu include Cynanchum auriculatum Royle ex Wight., Cynanchum bungei Decne. and Cynanchum wilfordii Hemsl. It is described in the Sign of Materia Medica as \"sweet, bitter, reinforce liver and kidney, and non-toxic\". It is widely used for nourishing the blood to expel wind, reinforcing liver and kidney, strengthening bones and muscles.
OBJECTIVE: In this review, the current research status of the C21 steroidal glycosides and their derivatives of Baishouwu for malignant tumours and their anti-tumour mechanisms are discussed. This may lay the ground for potential application of Baishouwu and its active ingredients in the treatment of tumours.
METHODS: Scientific databases, including PubMed, Elsevier, Science Direct, Google Scholar, CNKI, WANFANG DATA and VIP were searched to gather data about Baishouwu and its C21 steroidal glycosides and their derivatives.
RESULTS: Prior literature indicates that Baishouwu has important biological activities such as anti-tumour, anti-epileptic, reducing cholesterol, protection of liver and kidney and immunomodulatory, which are of increasing interest, especially its anti-tumour activity. Recent studies demonstrate that the C21 steroidal glycosides of Baishouwu, which have prominent antitumour efficacy, are one of its main active ingredients. Presently, a variety of C21 steroidal glycosides have been isolated from Baishouwu medicinal part, the tuberous root. This review summarizes the various antitumour activities of the C21 steroidal glycosides and their derivatives of Baishouwu.
CONCLUSIONS: In this review, the antitumour effects and mechanisms of total C21 steroidal glycosides and monomers and derivatives of Baishouwu in vitro and in vivo were summarized. Baishouwu can inhibit tumourigenesis by blocking tumour cell cycle progression, regulating numerous signaling pathways, promoting apoptosis, inhibiting tumour cells proliferation and metastasis, improving immunity and so on. This review provides a theoretical basis for inheriting and developing the medical heritage of the motherland, exploring the resources of traditional Chinese medicine for ethnic minorities and clinical rational drug use.

UNASSIGNED: Berberine (BBR), as one of the outstanding representatives of isoquinoline alkaloids, has been used as an antibacterial drug for a long time in China since ancient times. Currently, a large number of studies have been reported that berberine has a wide spectrum of pharmacological activities, such as anti-tumor, anti-inflammatory, hypoglycemic, hypolipidemic, anti-obesity, and the like.
UNASSIGNED: This review systematically discussed important patents on berberine and berberine derivatives in terms of pharmacological activity between 2016 and 2020. These patents were mainly searched through the European Patent Office database and Web of Science. These berberine patents (~41) cover a wide range of applications, mainly including antitumor, anti-inflammatory, antibacterial, anti-metabolic disorder, and other newly reported pharmacological activities.
UNASSIGNED: Berberine is an important lead compound with great potential for optimization in drug development. However, there is a lack of research related to the biomolecular targets of BBR, which directly restricts the development of berberine in the pharmaceutical field. The problems involved with poor bioavailability and cytotoxicity are also worth considering in the development of berberine-based drugs. Accordingly, the increasing number of patents involving biomolecular targets in BBR\'s patent applications will be published as its related pharmacological mechanisms are further deciphered.

Shikonin is the major bioactive component extracted from the roots of Lithospermum erythrorhizon which is also known as \"Zicao\" in Traditional Chinese Medicine (TCM). Recent studies have shown that shikonin demonstrates various bioactivities related to the treatment of cancer, inflammation, and wound healing. This review aimed to provide an updated summary of recent studies on shikonin. Firstly, many studies have demonstrated that shikonin exerts strong anticancer effects on various types of cancer by inhibiting cell proliferation and migration, inducing apoptosis, autophagy, and necroptosis. Shikonin also triggers Reactive Oxygen Species (ROS) generation, suppressing exosome release, and activate anti-tumor immunity in multiple molecular mechanisms. Examples of these effects include modulating the PI3K/AKT/mTOR and MAPKs signaling; inhibiting the activation of TrxR1, PKM2, RIP1/3, Src, and FAK; and regulating the expression of ERP57, MMPs, ATF2, C-MYC, miR-128, and GRP78 (Bip). Next, the anti-inflammatory and wound-healing properties of shikonin were also reviewed. Furthermore, several studies focusing on shikonin derivatives were reviewed, and these showed that, with modification to the naphthazarin ring or side chain, some shikonin derivatives display stronger anticancer activity and lower toxicity than shikonin itself. Our findings suggest that shikonin and its derivatives could serve as potential novel drug for the treatment of cancer and inflammation.

Curcumin is a pharmacologically active polyphenol derived from the popular spice element-Turmeric. The therapeutic activity of curcumin has been extensively investigated over the last few decades and reports suggest the role of curcumin in a large number of biological activities, particularly its prominent anticancer activity. Curcumin, being a pleiotropic molecule, is a regulator of multiple molecular targets which play crucial roles in various cell signaling pathways. It is known to suppress transformation, inhibit proliferation as well as induce apoptosis. However, despite all these benefits, the efficacy of curcumin remains limited due to its poor bioavailability, poor absorption within the systemic circulation and rapid elimination from the body. To overcome these limiting factors, researchers all around the world are working towards designing a synthetic and superior curcuminoid by making suitable structural modifications to the parent skeleton. These curcuminoids, mainly analogues and derivatives, will not only improve the physicochemical properties but also enhance the efficacy simultaneously. The present review will provide a comprehensive account of the analogues and derivatives of curcumin that have been reported since 2014 which have indicated a better anticancer activity than curcumin.

In recent years, the interest in studying modification of pectin has increased. A number of hydroxyl and carboxyl groups distributed along the backbone as well as a certain amount of neutral sugars presented as side chains make pectin capable of preparing a broad spectrum of derivatives. By forming pectin derivatives, their properties may be modified and some other new functional properties may be created. This article attempts to review the information about various methods used for pectin modification, including substitution (alkylation, amidation, quaternization, thiolation, sulfation, oxidation, etc.), chain elongation (cross-linking and grafting) and depolymerization (chemical, physical, and enzymatic degradation). Characteristics and applications of some pectin derivatives are also presented. In addition, the safety and regulatory status of pectin and its derivatives were reviewed.