A Review on Vanilla planifolia: From Traditional Cultivation to Modern Vanillin Applications, Pharmacological Activities, and Therapeutic Prospects

International Journal of Pharmaceutical Science and Health Care Volume 15, Number 5, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17360940 Original Article ©2025 RS Publication, rspublicationhou[email protected]m 146 “A Review on Vanilla planifolia: From Traditional Cultivation to Modern Vanillin Applications, Pharmacological Activities, and Therapeutic Prospects” Bandari Ramya*, Dr. G. Krishna Mohan 2 , Dr. M. Sandhya Rani. 3 Centre for Pharmaceutical Sciences, University College of Engineering, Science and Technology, Jawaharlal Nehru Technological University Kukatpally, Hyderabad– 500085, Telangana state, India. *Corresponding Author: Bandari Ramya ARTICLE INFO ABSTRACT ©2025 RS Publication Paper ID: IJPHC68E8CBA70592A Received: 2025-09-11 Published: 2025-10-11 DOI: https://dx.doi.org /10.5281/zenodo.17 360940 Page No: 146-159 Vanilla planifolia, or the vanilla orchid, is a tropical vine valued for its aromatic pods, which produce vanillin—the key compound responsible for vanilla’s flavour and fragrance. Beyond its culinary use, vanillin (4-hydroxy-3methoxybenzaldehyde) exhibits notable pharmacological activities, including antimicrobial, antioxidant, anticancer, anti-inflammatory, neuroprotective, and antisickling effects. Despite its therapeutic promise, vanillin’s medical application faces challenges such as poor oral bioavailability, rapid metabolism, and possible toxicity at high doses. Advances in microbial and biotechnological methods have improved vanillin production and led to the development of more stable and bioavailable derivatives. Vanillin is also widely used in cosmetics, perfumes, animal feed, and industrial applications, highlighting its multifunctionality. This review explores the biology of Vanilla planifolia, vanillin biosynthesis, pharmacology, safety concerns, and broad applications, while identifying research gaps and future directions for enhancing its therapeutic and commercial value. Keywords: Vanilla planifolia, Vanillin, Pharmacological activities, Bioavailability, Toxicity, Functional food. International Journal of Pharmaceutical Science and Health Care Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 Cite This Paper: Ramya bandari, Dr.G.Krishna Mohan and Dr.M.Sandhya Rani (2025). "A Review on Vanilla planifolia: From Traditional Cultivation to Modern Vanillin Applications, Pharmacological Activities, and Therapeutic Prospects". INTERNATIONAL JOURNAL PHARMACEUTICAL SCIENCE AND HEALTH CARE (IJPHC), vol. 15, no. 5, 2025, pp. 146-159. DOI: https://dx.doi.org/10.5281/zenodo.17360940 International Journal of Pharmaceutical Science and Health Care Volume 15, Number 5, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17360940 Original Article ©2025 RS Publication, rspublicationhou[email protected]m 147 Introduction Vanilla planifolia, often known as "flat-leafed" vanilla, is the scientific name for the plant that is widely known as "vanilla vine," "vanilla orchid," or just vanilla (1). After saffron, vanilla, a rich and distinctive fruit product of the Orchidaceae family, is the second most costly spice in the world. (2) The Spanish word "vanilla," which means "little pod," is where the term "vanilla" originated. Vanilla beans are sometimes known as pods or "black flowers" because, after harvested, the mature bean shrivels and turns black. (1) With more than 700 genera and 20,000 species, the Orchidaceae family is the biggest family of flowering plants, including this commercial and therapeutic orchid. Only the vanilla orchid has a commercial fruit, while many orchid species are cultivated for their blooms. (3) Description A thick, tropical, leafy, evergreen vine-climbing orchid with broad, meaty 6–9inch leaves, wild vanilla is indigenous to tropical regions. With the use of long, white, aerial roots that have a diameter of around 2 mm, it clings to the trees it climbs. (4,5) The trumpet-shaped blooms, which range in colour from white to yellow to green, are grouped along the vine. The three sepals measure 4–7 cm in length. Dried pods are shrivelled and black, but fresh pods are green and meaty. The axillary cluster that produces the blooms will contain 12–20 buds. (6) The blooms are greenish-yellow, 5 cm (2 in) in diameter, and have a faint fragrance. (7). Although pollination is necessary for the flowers to set fruit, they bloom in the morning and often fade in the afternoon as the temperature rises. (6) Although the flowers only persist for a single day, Vanilla planifolia flowers once a year over two months. (8) Around the conclusion of the dry season, in April and May, flowers bloom in the natural habitat of lowland forests. (9). Mature plants are the only ones that yield fruit. This takes three to four years for tissue cultures or 12inch cuttings, and two to three years for meter-long cuttings. The fruits are pods that are 15–23 cm (6–9 in) long and are frequently mislabelled as beans. They have the appearance of little bananas. It takes them eight to nine months to reach maturity. (8) Geographical description The ancient Mexican Totonaco Indians are where the history of vanilla starts. Vanilla was mostly produced in Mexico until the middle of the 19th century. The islands of Réunion and Mauritius received vanilla beans in 1819 by French. The world's five major growing regions International Journal of Pharmaceutical Science and Health Care Volume 15, Number 5, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17360940 Original Article ©2025 RS Publication, rspublicationhou[email protected]m 148 for vanilla are Madagascar, Indonesia, Mexico, Tahiti, and India. India has greatly increased its production in recent years, reaching about 24,000 hectares, with an estimated 700 tons of vanilla pods produced year. In the southern Indian states of Karnataka, Andhra Pradesh, Tamil Nadu, and Kerala vanilla plants are grown. (10,11) Cultivation and Harvesting The vanilla flower is hand-pollinated to develop the plant. Vanilla is grown in tropical climates and is spread via stem cuttings. The ideal temperature range is between 21°C and 32°C, with an average of 27°C. Rainfall needs range from 70 to 90 inches annually. Plant grows at altitudes up to 700 meters. It takes three to four years for the plant to begin blossoming, and then it blooms once a year. Before being harvested, the vanilla bean, a pod-like fruit, is given eight to ten months to grow. Vanilla beans have no taste and are picked green. A soil that has an abundance of accessible calcium and potassium is also necessary for healthy growth. It also favours soils with a pH of 6.0 to 7.0 and those that drain well. (2) The following step is to cure these beans. The curing procedure aids in the development of the vanilla taste. In order to facilitate the hydrolysis of precursor chemicals into vanillin, the flavour-adding component, interaction between flavour precursors and the enzymes is the primary goal of the curing procedures. Killing, perspiration, drying, and conditioning are the four main steps in the curing process. (12) Killing: By rupturing the tissues of green vanilla pods, this vital first step prevents their development and allows enzymes to engage with their targets. Although there are different ways to prepare them, beans are typically dipped in hot water. Sweating: The beans are stored in sealed bags or containers after being killed. This makes it possible for enzymes to produce vanillin and other substances that give vanilla its distinct flavour and scent. Drying and Conditioning: To maintain their scent, avoid mold, and get them ready for sale, beans are lastly dried and conditioned. The three criteria used to evaluate vanilla beans are moisture content, fragrance, and appearance. While fresh green beans have 75–82% moisture, high-quality beans are oily, deep brown, and longer than 12 cm. (3) International Journal of Pharmaceutical Science and Health Care Volume 15, Number 5, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17360940 Original Article ©2025 RS Publication, rspublicationhou[email protected]m 149 Figure:1 The stages of Vanilla planifolia cultivation and processing. (a) Vanilla planifolia plants are grown commercially in controlled environments; (b) hand pollination is used to ensure maximum bean production; (c) the beans are harvested when mature and then cured by (d) killing in scalding water, (e) sweating the beans in hot boxes or bags; (f) drying in sunlight; (g) bundling the beans for transporting and (h) marketing the beans. Extraction of Vanilla planifolia After being gathered, the leaves, stems, and pods of Vanilla planifolia were extracted using either water or ethanol as the solvent. Following the extraction procedure, particle debris was thoroughly filtered out of the resultant mixes. To eliminate the majority of the solvent, the filtrates were then concentrated by evaporation using a rotary evaporator at a lower pressure. The crude extracts were then freeze-dried to remove any remaining water and produce an entirely dry extract. In order to prepare them for further analysis or testing, the water extract was finally reconstituted in double-distilled water (ddH₂O), while the dried ethanol extract was finally redissolved in dimethyl sulfoxide (DMSO). (5) International Journal of Pharmaceutical Science and Health Care Volume 15, Number 5, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17360940 Original Article ©2025 RS Publication, rspublicationhou[email protected]m 150 Phytoconstituents Vanillin is the primary component of Vanilla planifolia; it is a methyl protocatechuic aldehyde (4-hydroxy-3-metoxybenzaldehyde) that makes up 85% of the total volatiles in vanilla beans. Several similar phenylpropanoid (C6–C3) chemicals are present in the vanillin-containing extract of Vanilla planifolia. These substances go through a number of enzyme processes during curing, which results in the distinctive flavour and fragrance of vanilla. Additional components mentioned include hydroxy benzoic acid, vanillic acid, anisaldehyde, anisic acid, anisyl alcohol, caproic acid, vitispiranes, eugenol, phenols, phenol ether, carbonyl compounds, acids, esters, benzyl ether, lactones, 25% are carbs, 15% are fat, the B complex, and the remaining 6% is made up of mineral salts including calcium, magnesium, zinc, manganese, potassium, and iron. Vanilla contains about 35% water. (13) Biosynthesis of vanillin Vanillin is made and stored in the vanilla pod as a harmless glucoside for protection. The exact biosynthesis pathway is still unclear, but Kundu (14) described some possible steps, including using coniferin as a precursor, CoA-dependent and non-CoA-dependent pathways, and direct conversion of ferulic acid to vanillin. Despite using efficient precursors, traditional plant extraction cannot meet global vanillin demand due to low yields, climate change, and complex processing. In fact, only about 0.2% of vanillin comes from natural sources, so chemical and microbial production methods are widely used. A. Chemical Production of Vanillin The primary aromatic component of vanilla, vanillin (3-methoxy-4-hydroxybenzaldehyde), is mostly in charge of its flavour and fragrance. Even though Figure 2 shows the currently recognized mechanism for vanillin production, there is ongoing discussion over this process. Alternative models are frequently proposed by new research without completely refuting the ones that already exist. (15) Phenylalanine, which is generated via the Shikimic acid pathway, is a precursor used in the natural production of vanillin. There are several ways that biosynthesis might take place, but p-coumaric acid is always synthesized. This can then be transformed (via a number of intermediates) into ferulic acid, caffeic acid, and vanillin. Alternatively, p-hydroxyaldehyde, an intermediary in two vanillin synthesis routes, may be produced directly from p-coumaric acid. Vanillin can be produced by directly methylating the p-hydroxyaldehyde in a process catalyzed by caffeic acid 5-hydroxyferulic acid International Journal of Pharmaceutical Science and Health Care Volume 15, Number 5, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17360940 Original Article ©2025 RS Publication, rspublicationhou[email protected]m 151 methyltransferase. However, it is thought that most of the p-hydroxyaldehyde is transformed into glucovanillin, which is then hydrolyzed to vanillin. Figure 2: Vanilla planifolia de novo pathway for the synthesis of vanillin from phenyl alanine. PAL=phenylalanine ammonia lyase; P450=cytochrome P450 system; 4CL=4 hydroxycinnamoyl-CoA ligase; HCT=hydroxy cinnamoyl transferase; COMT=cafeic acid 5hydroxyferulic acid O-methyltransferase; VpVAN=vanillin synthase. (3) International Journal of Pharmaceutical Science and Health Care Volume 15, Number 5, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17360940 Original Article ©2025 RS Publication, rspublicationhou[email protected]m 152 B. Microbial Production of Vanillin Microbial production of vanillin is preferred over chemical methods because it is cheaper and more eco-friendly. Many microorganisms, such as Pseudomonas, Amycolatopsis, Sphingomonas, Rhodococcus, Streptomyces, and E. coli, can make vanillin from ferulic acid. This process depends on two key enzymes, feruloyl-CoA synthetase (fcs) and enoyl-CoA hydratase/aldolase (ech), which convert ferulic acid into vanillin through a non-β-oxidative pathway. First, fcs changes ferulic acid into feruloyl-CoA, which is then broken down by ech into acetyl-CoA and vanillin. Recently, cheaper approaches using simple carbon sources like glucose, glycerol, or xylose have been developed. For example, genetically modified E. coli can produce vanillic acid from glucose via the shikimate pathway, and then convert it to vanillin using aryl aldehyde dehydrogenase. Similarly, engineered yeast strains such as Saccharomyces cerevisiae and Schizosaccharomyces pombe have been used with added genes to improve yields and reduce side reactions. (16). Figure 3: CoA-dependent conversion of ferulic acid to vanillin via a retro-aldol reaction. International Journal of Pharmaceutical Science and Health Care Volume 15, Number 5, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17360940 Original Article ©2025 RS Publication, rspublicationhou[email protected]m 153 Biological properties of vanillin Anticancer Activity A lot of research has shown that vanillin may help prevent or treat cancer. Early studies found that it reduced mutations caused by chemicals like methyl methane and mitomycin C in mouse bone marrow and fruit flies, by blocking their genotoxic effects and protecting against mutations. Vanillin also showed anti-mutagenic effects against other chemicals such as Nethyl-N-nitrosourea, N-methyl-N-nitrosourea, ethyl methane sulfonate, and bleomycin. Ho et al. (17) reported that vanillin stopped the cell cycle at the G2/M and G0/G1 stages and triggered cell death in HT-29 colon cancer cells, suggesting it could help prevent colorectal cancer. In Chinese hamster lung cells, vanillin reduced UV-induced mutations, chromosome abnormalities, and abnormal cell numbers. It also protected against genetic damage at the CD59 locus and blocked DNA-dependent protein kinase, helping repair damaged DNA. Additionally, vanillin inhibited the formation of harmful lung carcinogens from nitrosamines in mice. Overall, vanillin seems to block cancer development by preventing chromosome damage and related changes. Caveolin-1 (Cav-1) is a protein linked to cancer cell metastasis, so reducing its levels could help stop cancer spread. Vanillin was found to slow metastasis in human lung cancer cells by lowering Cav-1 expression. It also reduced MMP-9 enzyme activity in liver cancer cells (HepG2) by suppressing MMP-9 gene expression, which was connected to blocking the NF-κB signalling pathway. Shortand long-term treatment with vanillin reduced mutation rates in cells and downregulated cancer-related genes in liver cancer cells by lowering activator protein 1 activity and ERK phosphorylation, leading to apoptosis and cell cycle arrest. In human melanoma cells, vanillin showed cytotoxic effects and blocked NF-κB activation caused by chemotherapy drugs. (18) Antimicrobial Activity Studies show that vanillin has antimicrobial effects against bacteria, yeasts, and molds. It can inhibit microbes that spoil food, helping to extend shelf life in products like muffins, soft drinks, and cookies. Vanillin showed moderate antibacterial activity, with varying minimum inhibitory concentrations (MICs) against E. coli, Lactobacillus plantarum, and Listeria International Journal of Pharmaceutical Science and Health Care Volume 15, Number 5, 2025 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 DOI: 10.5281/zenodo.17360940 Original Article ©2025 RS Publication, rspublicationhou[email protected]m 154 innocua. (18) It also showed good antifungal activity against food-spoiling fungi and medically important yeasts like Candida albicans and Cryptococcus neoformans. (19) Vanillin derivatives, such as Schiff bases, showed even stronger antibacterial action against several Gram-positive and Gram-negative bacteria. Overall, vanillin is more effective against fungi than bacteria and can be used to preserve foods and as a base for making new antimicrobial agents. Antioxidant Activity Vanillin has strong antioxidant properties. In lab tests, it scavenged various free radicals (like DPPH, hydroxyl, and superoxide radicals) and inhibited lipid and protein peroxidation. It also reduced the formation of advanced glycation end products (AGEs) and protected mitochondria in rat liver. Animal studies confirmed these antioxidant effects. Vanillin (100–150 mg/kg) reduced oxidative stress caused by chemicals (like metribuzin, potassium bromate, and carbon tetrachloride), lowered markers of damage (such as MDA and protein carbonyls), and improved antioxidant enzyme activity. This suggests it can protect cell membranes and may help manage oxidative stress–related disorders, although human studies are still needed. (20) Anti-Inflammatory and Analgesic Activity Vanillin also shows anti-inflammatory and pain-relieving effects. In lab tests, it blocked NFκB activation, reduced COX-2 gene expression, and lowered production of inflammatory markers like nitric oxide and Inos (21). In animal studies, vanillin (50–200 mg/kg) reduced inflammation and swelling in rats and showed pain-relieving effects in mice when inhaled. It acted as a muscle relaxant without affecting normal behaviour. More studies are needed to fully confirm these effects, using tests like protein denaturation and membrane stabilization assays. (22) Anti-sickling Activity Vanillin has potential benefits for sickle cell disease. It prevents red blood cell sickling by binding to haemoglobin S and blocking certain ion channels. Its isomer, o-vanillin, and a prodrug version (MX-1520) showed even stronger anti-sickling effects due to better stability and bioavailability. Overall, vanillin and its derivatives could help reduce sickle cell complications by preventing abnormal red blood cell formation and improving oxygen delivery. (23)