PAEDERIA FOETIDA: INDIGENOUS MEDICINAL PLANTS OF NORTHEAST INDIA

Dakme Papi, Biplab Kumar Dey, Suman Saha and Ananta Choudhury Faculty of Pharmaceutical Science, Assam Downtown University, Panikhaiti, Guwahati, Assam. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History Received: 24 August 2021 Final Accepted: 27 September 2021 Published: October 2021

The plant Paederia foetida has customarily been utilized for restorative purposes, however, its system of helpful impacts has remained generally obscure. The northeastern locale of India comprises one of the biodiversity focal points of the world. The ethnic gatherings occupying this locale practice their particular customary information frameworks utilizing biodiversity for food and medical care. Among the less-concentrated plants, Paederia foetida has been utilized by different ethnic clans as food and medication. Many of its ethnobotanical properties relate to the hepatoprotective and gastrointestinal. This is a review of the ethnobotanical uses, phytochemistry, and therapeutic properties of Paederia foetida compiled from various reports. Paederia foetida is promising as a solution for the way of life-related conditions, particularly the treatment of liver cirrhosis. Its utility highlights the need for the evaluation of tribal plants as medicines and the species that could be considered for the development of new drugs.

…………………………………………………………………………………………………….... Introduction:-
The northeast region represents an important part of the Indo-Myanmar biodiversity hotspot and is one of the renowned 25 th global biodiversity regions. This area contains more than one-third of India's total biodiversity. Out of 450 tribal communities in India, the northeast states alone are the dwelling place of 225 ethnic communities 1 . These tribes have distinctive traditional knowledge systems based on the use of biodiversity for food, shelter, and health. Most of these plants are indigenous to this region and the knowledge base remains within the ethnic groups, there is a lack of awareness of these plants, accurate methods of preparation, edible and/or medicinal uses, and their active principles 2 . There is a need for prioritization of research on wild plants with detailed studies on active principles and nutritional components. An estimated 1600 plant species are used in Indian traditional systems of medicine, of which more than 80% are used in ethnomedicine in northeast India alone, indicating the rich traditional knowledge systems of northeast India 3 . Paederia foetida is one of 30 species in the genus Paederia in the family Rubiaceae is an extensive foetida smelling climbing plant 4 . It is mostly found in India, especially in the northeast state of Assam, Arunachal Pradesh, Tripura, Meghalaya, Manipur, Nagaland, and Sikkim, and in other countries such as China, Bangladesh, Japan, and Korea 5 . Different tribal communities from the North East to the South use the plant as a vegetable and treats various stomach disorders such as diarrhea and dysentery, as well as stomach swelling, to clean stomach, gastritis, in loose motion, indigestion, abdominal pain, etc... The leaf is additionally utilized as an enemy of ulcer specialist. Various scientific studies have been carried out to investigate the use of Paederia in the treatment of rheumatic affections, antiinflammatory, hepatoprotective, tripsyChemolithotripsy, promote sexual vigor, increases the quantity of semen 6,7 .

Phytochemical and Antioxidant of Paederia Foetida
The presence of polyphenolic compounds such as flavonoids, tannins, and terpenoids was discovered in a phytochemical screening of Paederia foetida extract, and previous research revealed that the leaves are high in antioxidant compounds such as carotene and vitamin C 8 . The extract of Paederia foetida contains antioxidant compounds that can scavenge free radicals such as DPPH. By scavenging free radicals, phenolic compounds protect various organs of the body from damage and disease, while also maintaining normal human health. Tannins are found in many different plants 9 . Anticarcinogenic, antimutagenic, and antimicrobial properties have all been reported. Flavonoids and tannins may protect plants from pathogenic microorganisms due to their antimicrobial and antifungal properties 10,11 . Polyphenols and tannins have antimicrobial properties due to their ability to inhibit enzymes, disrupt membranes, and form metal ion complexes. Alkaloids have antimicrobial properties due to their ability to intercalate into parasite cell walls and DNA. Paederia foetida was able to infect both gram-positive and gram-negative bacteria 12 . The antibacterial action of Paederia foetida might be ascribed to Polyphenols, flavonoids, tannins, and alkaloids 13 .

Traditional Uses in Food and Medicine in Northeast India
The plant is traditionally administered in a variety of forms by tribal peoples in the Northeast, depending on their needs/ailments 14 . For medicinal purposes, a decoction of the whole plant, leaf, stem, stem bark, or leaf juice is prepared. Tender leaves are boiled and served with Chile and salt as a meal 15 . Certain ethnic groups in India's Assam state cook the leaves with rice to treat rheumatism and gout, among other joint diseases. Tripura clan makes 'Gudak' with dry fish and Paederia foetida leaves 16 . The Nyishi tribes of Arunachal Pradesh use leaf juice to treat diarrhea, dysentery, and burns or scalding 17 . Certain tribal communities in other parts of India have also reported using the whole plant powder to treat weakness and rheumatoid joint pains. Its nutritional and medicinal value is enhanced by high levels of protein (5%), fat (1%), carbohydrate (3%), dietary fiber, minerals (potassium, magnesium, nitrogen, manganese, natrium, calcium, zinc, copper, phosphorus, and iron), vitamin C, and phenolic content 18,19 . The traditional uses of Paederia foetida are listed in Table 1.

Pharmacological Activities and Mechanism of Action of Paedria Foetida Hepatoprotective activity:
The hepatoprotective activity of a 70% ethanolic extract of Paederia foetida leaf in paracetamol-induced liver damage in a rat model. The anti-hepatotoxin potential of the plant extract was then tested in vitro against paracetamol-induced hepatic lesions. Extracts of Paederia foetida significantly increased serum glutamate-pyruvate aminotransferase (SGPT), total protein, and serum glutamate-oxaloacetate transaminase levels at doses of 50,200, and 400 mg/kg body weight of rat (SGOT). The plant extract significantly reduced hepatic lipid peroxide (LPO) levels in the paracetamol-induced rat by 40%. Other studies have discovered that it has a moderate hepatoprotective effect, implying that it could be used to treat a wide range of liver disorders 32 .

Anti-inflammatory activity:
The anti-inflammatory activity of the butanol fraction of a methanol extract of the defatted leaves of Paederia foetida produced a more potent inhibition of granulation tissue formulation in cotton-pellet implanted rats 33 . It reduced liver aspartate transaminase activity but did not affect serum aspartate transaminase activity. The percentage of anti-inflammatory activity of P. foetida was shown to be dose-dependent. At two different dosages of 20.5 and 41 mg/kg -1 , the percentages of anti-inflammatory activity were 38.55 and 48.97 respectively, which was stronger than acetylsalicylic acid (37.5% of anti-inflammatory activity at a dosage of 50 mg/kg -1 ) but weaker than hydrocortisone (61.46% of anti-inflammatory activity at a dosage of 0.5 mg/kg -1 ) 34 .

Antitussive activity:
In awake cats, an ethanolic extract of Paederia foetida was used to stimulate the laryngopharyngeal and tracheobronchial mucosal. With an oral dose of 200 mg/kg-1 b.wt. cough suppression. The anti-tussive activity of Paederia foetida ethanolic extract was lower than that of a traditional narcotic anti-tussive medicine but comparable to that of a non-narcotic anti-tussive agent (dropropizine) 35 .

Anti-ulcer activity:
There are numerous scientific and traditional claims about the benefits of Paederia foetida for gastrointestinal tract illnesses such as dysentery, stomach swelling, piles, abdominal discomfort, diarrhea, gastralgia, and other maladies such as gastritis or ulcer 36 . In rats, anti-ulcer screening was performed using two methods: pyloric ligation and aspirin-induced ulcerations. As a result, the roots of Paederia foetida are said to have anti-ulcer properties, which may be attributed to the expected suppression of H2 receptors, which inhibit gastric acid release induced by histamine and gastrin 37 .

Anti-diarrheal activity:
The 70 percent ethanolic extract of Paederia foetida demonstrated anti-diarrheal activity in rats using castor oil and magnesium sulfate-induced diarrhea. The activity is caused by a decrease in gastrointestinal motility and a significant lengthening of the diarrhoeal latent period 38 . In the castor oil study, the purging index (PI) value decreased after 1 hour at doses of 50, 200, and 400 mg/kg 39 . Only at 500mg/kg did the effect last for 6 hours. The plant significantly reduced the purging index value in magnesium sulfate-induced diarrhea in a dose-dependent manner. In the castor oil study, the purging index (PI) value decreased after 1 hour at doses of 50, 200, and 400 mg/kg. Only at 500mg/kg did the effect last for 6 hours. The plant significantly reduced the purging index value in magnesium induced diarrhea in a dose-dependent manner 40 .

Anthelmintic activity:
A methanolic extract of Paederia foetida leaves was tested for anthelmintic activity against Pheretima Posthuma and Tubifex. Paederia foetida completely eradicated Bunostomum sp. and Monezia sp. Over a week, at two-day intervals, at a dosage of 4-10 oz. based on body weight 41 .

Analgesic activity:
Analgesic activity was assessed in mice using the acetic acid-induced writhing inhibition method, and at a dose of 150 mg. kg p.o., considerable antinociceptive activity was detected. Hexane, ethyl acetate, and methanolic extract inhibited the enzyme by 21%, 9%, and 19%, respectively 42 . 50 mg/kg aminopyrine inhibited writhing by 63% in the same experiment. Analgesic action was thought to be caused by blocking the prostaglandin pathway 43 .

Antibacterial activity:
The test includes two Gram-positive bacteria (Staphylococcus aureus and Enterococcus faecalis) and three Gramnegative bacteria (Escherichia coli, Salmonella typhimurium 44 . The extract exhibited antibacterial activity against S.flexneri, S.aureus, E.coli, and E.faecalis. As per the early screening preliminary, S.flexneri was the weakest microorganisms. S. typhimurium was the safest. The experiment results clearly show that the Paederia foetida plant has antibacterial properties 45 .

Anti-arthritic activity:
Arthritis is a chronic inflammatory disease that affects the joints as well as the tissues that surround them. Paederia foetida was found to be more effective in treating rheumatoid arthritis than Merremia tridentate, a South Indian medicinal plant used for the same condition. The plant can also reduce high levels of acute-phase proteins, making it disease-modifying drugs (NSAIDs), which do not affect these proteins 46 .

Anticancer activity:
The plant can also lower high levels of acute-phase proteins, making it a disease-modifying anti-rheumatic drug (DMARD) with advantages over NSAIDs, which do not affect these proteins 47 . The plant has anticancer properties, according to Bangladesh folk medicine. The traditional use of 50% ethanolic extract as an anticancer drug was justified after it was shown to have anticancer activity in tissue culture against human nasopharyngeal. This activity could be attributed to its anti-inflammatory or antioxidant properties 48,49 .

Anti-nociceptive activity:
Many pharmacological studies have shown that these two plants are effective pain relievers in folk medicine. At 300 mg/kg body weight, hexane and methanol extracts of Paederia foetida demonstrated significant anti-nociceptive efficacy in Swiss albino mice, with 37.4% & 25% decreases in the number of writhing elicited by acetic acid, respectively 50 . To test potential anti-nociceptive pathways, several receptors and ion channel blockers were used, including naloxone, glibenclamide, nimodipine, and L-NAME. PEF-induced antinociception was linked to glibenclamide-sensitive K+-ATP channels, whereas BF primarily inhibited antinociception via nimodipine-sensitive L-type Ca2+ channels 51,52 . Paederia foetida is mostly made up of fatty acids (linoleic acid) and sterols (stigmasterol and -sitosterol), both of which have been linked to analgesic properties. The n-butanol fraction contains a high concentration of iridoid glycosides, which prompted us to investigate the analgesic properties of these chemicals 53,54 .

Effect on digestive system:
Several studies have shown that Paederia foetida is effective in the treatment of digestive disorders. In India, a decoction of Paederia foetida leaves and shoots (30 ml, 10 g in 100 ml water) is used to treat abdominal colic and gastric ulcers, while worms are treated with a decoction of fresh crushed root (10 g in 100 ml water) 55 . In Mauritius, Paederia foetida, an alien plant, is used to cure ulcers and other ailments 56 . In Assam 57 , the aerial portions of Paederia foetida were used to treat diarrhea and dysentery, and a decoction of the leaves was used orally to relieve stomachaches. Anti-ulcer and anti-inflammatory properties were also found in the leaf extract 58 . Paederia foetida (500 mg/kg) had a significant antidiarrheal ability in mice in the castor oil and magnesium sulfate-induced diarrhea models, which justified its traditional use in the treatment of diarrhea 59 . Furthermore, the juice of Paederia foetida leaves (8%) had a prophylactic effect in rats against ethanol-induced stomach ulcers 60,61 . The root extract of Paederia foetida was recently shown to have strong anti-ulcer efficacy in lowering gastric acid output and thus preventing ulceration in rats caused by pyloric ligation and aspirin, which justified its traditional use in folk medicine 62 .

Antioxidant activity:
The antioxidant activity of fresh and dried Paederia foetida plant extracts was investigated using -carotene bleaching and the 2, 2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation test 63 . Using both assays, the percentage of antioxidant activity of fresh samples ranged between 58 and 80 percent, while the percentage of antioxidant activity of dried samples ranged between 68 and 6 percent. The presence of vitamin C as one of the metabolites may contribute to its antioxidant properties. Another study using the DPPH assay discovered free radical scavenging activity with an IC50 value of 4.53 mg/ml 64 .

Conclusions:-
Paederia foetida is widely used as a medicinal plant, but studies show that it can also be eaten. It is one of the most popular vegetables among tribal communities in Northeast India. The plant extract has several medicinal properties, the most common of which are hepatoprotective. Other therapeutic benefits include gastrointestinal diseases, antiinflammatory properties, arthritic properties, analgesics, and antioxidants, among others. Paederia foetida extract could be studied further in the future as a source of beneficial phytochemicals for the pharmaceutical industry.