An In Vitro Examination of Whether Kratom Extracts Enhance the Cytotoxicity of Low-Dose Doxorubicin against A549 Human Lung Cancer Cells.

Doxorubicin is an effective chemotherapeutic agent in the treatment of solid hematological and non-hematological carcinoma. However, its long-term usage could result in side effects, such as cardiomyopathy, chronic heart failure, neurotoxicity and cancer cell resistance. In this study, we reported the sensitivity enhancement of A549 human lung cancer cells on doxorubicin at a low dose (0.1 ppm) in combination with 10-60 ppm of crude and alkaloid extracts derived from the leaves of Kratom (Mitragyna speciosa (Korth.) Havil. Rubiaceae). A549 cancer cell lines were insensitive to the crude extract containing low mitragynine (MG) (4-5%), while these cells were moderately inhibited by the alkaloid extract containing 40-45% MG (IC50 of 48-55 ppm). The alkaloid extract was found to inhibit A549 cancer cells via apoptosis as suggested by the higher relative fluorescence intensity with Annexin compared to that in propidium iodide (PI), i.e., a positive Annexin and a negative PI. The combination of crude extract and doxorubicin sensitized A549 cancer cells to doxorubicin by 1.3 to 2.4 times, while the combination with the alkaloid induced a 2.6- to 3.4-fold increase in sensitivity. The calculated combination index (CI) for doxorubicin with the crude and alkaloid extracts was 0.6 and 0.3, respectively, showing potential synergistic combinations to reduce the level of dosage of doxorubicin used in chemotherapy. In addition, the synergistic enhancement effect of crude extract on the cytotoxic activity of doxorubicin provides insights into the plausibility of non-alkaloids to influence the biological activities of Kratom.

Ircinia ramosa Sponge Extract (iSP) Induces Apoptosis in Human Melanoma Cells and Inhibits Melanoma Cell Migration and Invasiveness.

Marine compounds represent a varied source of new drugs with potential anticancer effects. Among these, sponges, including those belonging to the Irciniidae family, have been demonstrated to exert cytotoxic effects on different human cancer cells. Here, we investigated, for the first time, the therapeutic effect of an extract (referred as iSP) from the sponge, Ircinia ramosa (Porifera, Dictyoceratida, and Irciniidae), on A375 human melanoma cells. We found that iSP impaired A375 melanoma cells proliferation, induced cell death through caspase-dependent apoptosis and arrested cells in the G1 phase of the cell cycle, as demonstrated via both flow cytometry and qPCR analysis. The proapoptotic effect of iSP is associated with increased ROS production and mitochondrial modulation, as observed by using DCF-DHA and mitochondrial probes. In addition, we performed wound healing, invasion and clonogenic assays and found that iSP was able to restrain A375 migration, invasion and clonogenicity. Importantly, we observed that an iSP treatment modulated the expression of the EMT-associated epithelial markers, E-CAD and N-CAD, unveiling the mechanism underlying the effect of iSP in modulating A375 migration and invasion. Collectively, this study provides the first evidence to support the role of Ircinia ramosa sponge extracts as a potential therapeutic resource for the treatment of human melanoma.

Cutting Edge Aquatic-Based Collagens in Tissue Engineering.

Aquatic-based collagens have attracted much interest due to their great potential application for biomedical sectors, including the tissue engineering sector, as a major component of the extracellular matrix in humans. Their physical and biochemical characteristics offer advantages over mammalian-based collagen; for example, they have excellent biocompatibility and biodegradability, are easy to extract, and pose a relatively low immunological risk to mammalian products. The utilization of aquatic-based collagen also has fewer religious restrictions and lower production costs. Aquatic-based collagen also creates high-added value and good environmental sustainability by aquatic waste utilization. Thus, this study aims to overview aquatic collagen's characteristics, extraction, and fabrication. It also highlights its potential application for tissue engineering and the regeneration of bone, cartilage, dental, skin, and vascular tissue. Moreover, this review highlights the recent research in aquatic collagen, future prospects, and challenges for it as an alternative biomaterial for tissue engineering and regenerative medicines.

Secondary Metabolites from Marine-Derived Fungi and Actinobacteria as Potential Sources of Novel Colorectal Cancer Drugs.

Colorectal cancer is one of the most common cancers diagnosed in the world. Chemotheraphy is one of the most common methods used for the pharmacological treatment of this cancer patients. Nevertheless, the adverse effect of chemotherapy is not optimized for improving the quality of life of people who are older, who are the most vulnerable subpopulation. This review presents recent updates regarding secondary metabolites derived from marine fungi and actinobacteria as novel alternatives for cytotoxic agents against colorectal cancer cell lines HCT116, HT29, HCT15, RKO, Caco-2, and SW480. The observed marine-derived fungi were from the species Aspergillus sp., Penicillium sp., Neosartorya sp., Dichotomomyces sp., Paradendryphiella sp., and Westerdykella sp. Additionally, Streptomyces sp. and Nocardiopsis sp. are actinobacteria discussed in this study. Seventy one compounds reviewed in this study were grouped on the basis of their chemical structures. Indole alkaloids and diketopiperazines made up most compounds with higher potencies when compared with other groups. The potency of indole alkaloids and diketopiperazines was most probably due to halogen-based functional groups and sulfide groups, respectively.

Antiviral Activities of Algal-Based Sulfated Polysaccharides.

An antiviral agent is urgently needed based on the high probability of the emergence and re-emergence of future viral disease, highlighted by the recent global COVID-19 pandemic. The emergence may be seen in the discovery of the Alpha, Beta, Gamma, Delta, and recently discovered Omicron variants of SARS-CoV-2. The need for strategies besides testing and isolation, social distancing, and vaccine development is clear. One of the strategies includes searching for an antiviral agent that provides effective results without toxicity, which is well-presented by significant results for carrageenan nasal spray in providing efficacy against human coronavirus-infected patients. As the primary producer of sulfated polysaccharides, marine plants, including macro- and microalgae, offer versatility in culture, production, and post-isolation development in obtaining the needed antiviral agent. Therefore, this review will describe an attempt to highlight the search for practical and safe antiviral agents from algal-based sulfated polysaccharides and to unveil their features for future development.

Marine-Derived Indole Alkaloids and Their Biological and Pharmacological Activities.

Novel secondary metabolites from marine macroorganisms and marine-derived microorganisms have been intensively investigated in the last few decades. Several classes of compounds, especially indole alkaloids, have been a target for evaluating biological and pharmacological activities. As one of the most promising classes of compounds, indole alkaloids possess not only intriguing structural features but also a wide range of biological/pharmacological activities including antimicrobial, anti-inflammatory, anticancer, antidiabetic, and antiparasitic activities. This review reports the indole alkaloids isolated during the period of 2016-2021 and their relevant biological/pharmacological activities. The marine-derived indole alkaloids reported from 2016 to 2021 were collected from various scientific databases. A total of 186 indole alkaloids from various marine organisms including fungi, bacteria, sponges, bryozoans, mangroves, and algae, are described. Despite the described bioactivities, further evaluation including their mechanisms of action and biological targets is needed to determine which of these indole alkaloids are worth studying to obtain lead compounds for the development of new drugs.

Chemical Diversity and Biological Activity of Secondary Metabolites Isolated from Indonesian Marine Invertebrates.

Marine invertebrates have been reported to be an excellent resource of many novel bioactive compounds. Studies reported that Indonesia has remarkable yet underexplored marine natural products, with a high chemical diversity and a broad spectrum of biological activities. This review discusses recent updates on the exploration of marine natural products from Indonesian marine invertebrates (i.e., sponges, tunicates, and soft corals) throughout 2007-2020. This paper summarizes the structural diversity and biological function of the bioactive compounds isolated from Indonesian marine invertebrates as antimicrobial, antifungal, anticancer, and antiviral, while also presenting the opportunity for further investigation of novel compounds derived from Indonesian marine invertebrates.

Evaluations of Andrographolide-Rich Fractions of Andrographis paniculata with Enhanced Potential Antioxidant, Anticancer, Antihypertensive, and Anti-Inflammatory Activities.

Andrographis paniculata is widely used as a traditional medicine in Asian countries. It has been classified as a safe and non-toxic medicine by traditional Chinese medicine. The investigation of the biological activities of A. paniculata is still focused on the crude extract and isolation of its main active compound, andrographolide, and its derivatives. However, the use of andrographolide alone has been shown to exacerbate unwanted effects. This highlights the importance of developing a fraction of A. paniculata with enhanced efficacy as an herbal-based medicine. In this study, the extraction and fractionation of A. paniculata, followed by quantitative analysis using high-performance liquid chromatography coupled with a DAD detector, were established to quantify the andrographolide and its derivative in each fraction. Biological activities, such as antioxidant, anticancer, antihypertensive, and anti-inflammatory activities, were evaluated to study their correlations with the quantification of active substances of A. paniculata extract and its fractions. The 50% methanolic fraction of A. paniculata exhibited the best cytotoxic activities against CACO-2 cells, as well as the best anti-inflammatory and antihypertensive activities compared to other extracts. The 50% methanolic fraction also displayed the highest quantification of its main active compound, andrographolide, and its derivatives, 14-deoxy-11,12-didehydroandrographolide, neoandrographolide, and andrograpanin, among others.

Antiviral Activities of Andrographolide and Its Derivatives: Mechanism of Action and Delivery System.

Andrographispaniculata (Burm.f.) Nees has been used as a traditional medicine in Asian countries, especially China, India, Vietnam, Malaysia, and Indonesia. This herbaceous plant extract contains active compounds with multiple biological activities against various diseases, including the flu, colds, fever, diabetes, hypertension, and cancer. Several isolated compounds from A. paniculata, such as andrographolide and its analogs, have attracted much interest for their potential treatment against several virus infections, including SARS-CoV-2. The mechanisms of action in inhibiting viral infections can be categorized into several types, including regulating the viral entry stage, gene replication, and the formation of mature functional proteins. The efficacy of andrographolide as an antiviral candidate was further investigated since the phytoconstituents of A. paniculata exhibit various physicochemical characteristics, including low solubility and low bioavailability. A discussion on the delivery systems of these active compounds could accelerate their development for commercial applications as antiviral drugs. This study critically reviewed the current antiviral development based on andrographolide and its derivative compounds, especially on their mechanism of action as antiviral drugs and drug delivery systems.

Cembranoids of Soft Corals: Recent Updates and Their Biological Activities.

Soft corals are well-known as excellent sources of marine-derived natural products. Among them, members of the genera Sarcophyton, Sinularia, and Lobophytum are especially attractive targets for marine natural product research. In this review, we reported the marine-derived natural products called cembranoids isolated from soft corals, including the genera Sarcophyton, Sinularia, and Lobophytum. Here, we reviewed 72 reports published between 2016 and 2020, comprising 360 compounds, of which 260 are new compounds and 100 are previously known compounds with newly recognized activities. The novelty of the organic molecules and their relevant biological activities, delivered by the year of publication, are presented. Among the genera presented in this report, Sarcophyton spp. produce the most cembranoid diterpenes; thus, they are considered as the most important soft corals for marine natural product research. Cembranoids display diverse biological activities, including anti-cancer, anti-bacterial, and anti-inflammatory. As cembranoids have been credited with a broad range of biological activities, they present a huge potential for the development of various drugs with potential health and ecological benefits.