A Review Antimicrobial Mechanisms of Polyherbal Extracts: Role of Phenolics, Flavonoids, and Alkaloids

Indian medicinal plants are found to be good sources of bioactive compounds in the form of polyphenols and alkaloids, which contain strong antimicrobial activity. The phytochemicals are reported to play important roles in countering bacterial, fungal, and viral infections through microbial cell wall targeting, interruption of enzyme processes, and preventing biofilm production. The rising global interest in antimicrobial resistance (AMR) has led to increased studies of natural substitutes, and polyphenols and alkaloids are showing great promise as new antimicrobial drugs. People have been looking for healing substance in plants for a very long time. Today, this search has become more important because many antibiotics are losing their effectiveness. This happens for several reasons-antibiotics don’t take them properly, they are often used carelessly in farming, and new antibiotics are being developed too slowly. As a result, more and more germ are becoming resto treatment stance.[1]

Plants have long been an important source of natural compounds used to treat many diseases. Studying and identifying the chemical found in herbs has helped scientists discover new medicines. In fact, about about 11% of all essential drugs around the world come directly from plants. Unlike synthetic drugs, natural plant-based treatments often show anti inflammatory antioxidant, and anticancer effects in different ways – and they tend to be safer for patients, with fewer or no side effects.[2] Many studies have explored how herbs fight bacteria, including which types of microbes they of microbes they affect and how their antibacterial components work. The research discussed in this review comes from well know scientific database like PubMed, ScienceDirect, Web of science, EBSCO OVID, and Wiley online library.[3]

PHENOLICS:

Structure and antimicrobial mechanisms:

Polyphenols are a group of natural compounds found in many plants. They're the most common plant-based chemicals known for their positive effects on health.[4] Phenolic compound are a large and varied group of substance found in many edible plants. Early research mainly looked at their potential to cause genetic damage, but later studies showed that they can actually help prevent many common diseases in western societies. These compounds act as antioxidants –they can directly protect the body from damage caused by harmful molecules, and they can also boost the body’s own protective enzymes and help regulate important cell processes.[5] Phenolic antioxidants are the only type of compounds in this group that have been carefully tested to see how well they kill or stop the growth of germs. Different kinds of phenolic compounds vary a lot in how effective they are against certain bacteria, fungi and viruses. Scientist have studied how these compounds work but they still don’t completely understand the exact way they do it. This review looks at what research has found about about which microbes these compounds can fight and how they might work.[6]

Cell wall and membrane disruption:

The scientists suggest that in order for the rust fungus to successfully infect the plant, it might actually try to weaken that bond (the adhesive) between the plant’s cell wall and its inner membrane. By loosening that crucial connection, the fungus could be “jamming” or shutting down the plant’s basic immediate defence response as it pushes its way into the host cell.[7]

The cell wall is the strong, protective box that sits just outside the balloon’s skin (called the plasmalemma).

Think of this “(the cell wall) as a kind of fiberglass made up of two main parts:

Tiny ropes (the dispersed phase): These are extremely fine, strong threads made of cellulose, called microfibrils. They provide the main structure and strength.

A sticky filler ( the continuous matrix): This is a complex, gel-like substance that surrounds and glues the cellulose ropes together, making a continuous, solid wall. The cell wall is not static, its always changing.

Young walls: in young, growing plants, the walls are mostly made of sugars and a special structure protein that’s high in a component called hydroxyproline. They are very dynamic, meaning they change rapidly.

Older walls: as plants mature, they often add another hard woody substance called lignin to the wall.

Protein and enzymes inhibition:

Phenolic compound, which are natural substance found in many plants, ca significantly interferes with how your body digest protein. This negative effect occurs primarily because these compounds bind to critical components within your digestive system. On one hand, they attach themselves to your body’s own protein, most importantly the digestive proteases (the enzymes responsible for breaking down food). This binding drastically reduces the activity of these crucial enzymes, making them self-efficient at their job. On the other hand, phenolic compounds also Strick to the protein you eat, essential creating a barriers that makes the protein harder for the digestive enzymes to reach. Ultimately, by influencing both enzymes function and the accessibility of food protein, these compound act as major factors that decrease the overall efficiency of digestibility.[8]

Molecular interaction are classification as either reversible or reversible interaction are temporary connection formed by non-covalent forces such as hydrogen bonding, hydrophobic bridging, van der waals forces, and ionic interaction in contrast, irreversible interaction involve covalent bonds, which are permanent chemical linkages. The mechanism for forming these irreversible involves covalent bonds, which are promoted by a phenolic compound (PC), which uses its characteristic structure to produce a quinone radical. This quinone radical derived, from the oxidation of the phenolic moiety, is highly reactive and drives the covalent bond formation.[9]

Metal ion chelation

Metals and their ions are absolutely essential in our daily lives and play a crucial role in many different biological processes, such as photosynthesis, how protein fold the transmission of nerve signals, and even how marine organism stick underwater. These natural systems that use metals offer great inspiration for chemists to design new synthetic material with specific, useful characteristics. A particularly popular class of these material, called hybrid metal organic material.[10]

Metal ions are essencial for living things to carry out their most basic biological functions. However, for thousands of years, human have used metals widely in everyday life without paying attention to the harmful effects this usage might cause. Consequently, this has led to significant metal pollution, which is not only destroying entire ecosystems but is also contaminating our water sources and seriously impacting both plant and animal life.[11]

Oxidative stress induction:

The health benefits of polyphenols- like their ability damage (antioxidant) and reduce swelling (anti-inflammatory) effects –are mostly due to fight damage their unique chemical makeup specially, their structure, their structure includes a ring shapes (aromatic feature) and a highly stable network of alternating bonds (conjugated system) along with several attracted hydroxyl groups (OH groups). This structure makes them excellent at donating electrons or hydrogen atoms, which allows them to effectively neutralize harmful molecules like free Radiac and other reactive oxygen species there protecting the body.[12] The creation of reaction oxygen species those potentially harmful molecules is a normal built in process in body and its kept in check by the body’s own antioxidant system cell are naturally equipped with a wide variety of protective antioxidants both those made of enzymes and those that are non- enzymatic all designed to fight against and neutralize any oxidising agents that could cause damage.[13] Oxidative stress occurs when there is a massive buildup of harmful molecules called reactive oxygen species. This harmful accumulation can be trigged by a wide variety of factor including exposure to radiation,  attack by disease-causing agents (pathogen invasion)the natural process of aging various disease and exposure to heat stress.[14]Flavonoids are a diverse group of natural compounds found throughout the plant kingdom including in common foods and beverages like. Fruits, vegetables, grains, bark, roots, flowers, tea, and wine. These substances are al based on a varied phenolic structure. Flavonoids are famous for their positive effects on health, which is why a lot of effort is currently focused on isolating them as individual ingredients for use in supplement or medicine.[15]

Inhibition of nucleic acid synthesis:

four specific flavonoids –baicalein, quercetin, quercetagetin, and myricetin-are already known to block the enzymes HIV-reverse transcriptase which the HIV virus to copy itself. Researchers have found that these same four compound can to varying degrees inhibit or slow down the activity of several other key enzymes found in own cells the DNA and RNA polymerases which our cells use to copy our genetic material.[16]

Membrane permeability alteration:

Researchers looked at eight natural flavonoids that are chemically similar to one another to see how well they could protect the energy –producing parts of a cell mitochondria taken from rat livers. They specially measured the flavonoids ability to inhibits block or slow down four damaging process lipid peroxidation damage to fast mitochondria membrane permeability transition met which is when the mitochondria membrane breaks down and the degradation of two essential mitochondria function respiration and the oxidation of protein sulfhydryl group.[17]

Quorum sensing inhibition:

In nature many different organisms live together in the same place. It’s now well understood that bacteria primarily communicate with each other to cooperate within their groups, but also to complete against silencing the communication system of their rivals –known as the quorum sensing (QS) system –using a wide a wide variety of chemical compounds.[18] It is widely understood that when microorganism grow in a biofilm a protective layer they create they become much harder to kill with antimicrobial agents. Scientists have published many studies discussing how quorum sensing QR the system bacteria use to communicate is involved in the creation of these biofilms. However, the current research presents conflicting conclusion on exactly how important QR is to the overall process of bacteria biofilm formation.[19]

Synergy with antibiotics:

In most of the studies reviewed 25 out of 41 researchers defined synergy meaning the combination works better than either drug alone –by using a specific calculation called the fractional inhibitory concentration index fici. The fici is determined by adding two ratios (1) the minimum inhibitory concentration mic of when used with another antibiotic divided by the mic of fosfomycin used by itself. Essentially, this formula compares how much less of each drug is needed to stop bacterial growth when they are used together.[20]

It protect itself successfully and efficiently transmit signals to start the process of accumulating these protective alkaloids.[21]

Interference with cell division and metabolism:

Cell division is an absolutely essential and fundamental part of the cell life cycle for all living things. Many years of dedicated research scientists still don’t fully understand this complex process previously, a critical called ObgE- a type of gtpase that is involved in many basic cell function like starting DNA coping separating chromosome and building ribosome –was suggested to act as a checkpoint in bacteria in this proposed role it would essentially licence or authorize the cell to proceed with chromosome segregating the separation od genetic material at the right time.[22]

Membrane disruption:

Cell communication and manage information using molecules, much like computer chips process data using electronic signals. In this system, the flow of information starts with DNA which holds the blueprints for creating RNA and protein. The protein are the workhorses of the cell they carry out essential tasks, send and receive signals throughout the cell, and serve as the structural components that build and organize the cell itself. The cell membrane which acts as the cell outer barrier plays a critical role in controlling this exchange selectively allowing molecules in and out.[23]

ALKALOIDS:

Alkaloids are one of the largest families of compounds produced by plants that aren’t necessary for primary growth secondary metabolites, and they are found in many economically important crops. This group includes well known neuroactive molecules like caffeine and nicotine as well as lifesaving medicine such as emetine used for poisoning and the antitumor drugs vincristine vinblastine in plants alkaloids primarily function as defence compounds because  their toxicity makes them highly effective against invading pathogens diseases and predators for a plants. Alkaloids are a very large and varied group of naturally occurring chemical compounds found only in certain organism that process important biological effects these complex substance are defined by a specific structure they ring shaped compounds that contain a nitrogen atom in a particular electrical state.[24]

Biofilm inhibition:

The ability of disease-causing bacteria to form a protective community called a biofilm within a host is a major problem, as it makes them highly tolerant to antibiotics and allow for the creation of tough, dormant cell called persisters. This often leads tp treatment failure and recurring choric infection as a result, scientists are urgently looking for new drugs that can either specially stop the formation of these biofilms or active breaks apart nature ones by getting rid of the biofilm structure, these new agents would allow standard antibiotics to effectively reach and kill the sensitive bacteria inside. This mini review aims to examine various chemical strategies using small molecules that have been developed to inhibit bacteria biofilm formulation at different stages of its development.[25]

?SYNERGISTIC ACTION IN POLYHERBAL FORMULATIONS:

Researchers the combined effect of the ingredient in a polyherbal formulation a medicine made for multiple herbs on its antioxidants always its used comparison and difference methods they found that two specific herbs, the highest levels of total phenolic content and consequently showed the strongest antioxidant power when tested individually interestingly the antioxidant activity of the complete polyherbal formulation itself was only in the middle range of the value observed for its individual components.[26]

Target multiple microbial pathway:

This review will explore the complex methods that microbes like bacteria, fungi, use to interfere with a plants main defence system the salicylic acid pathway which ultimately helps them cause disease we look at how these microbes specifically target three areas blocking the creation of signal transduction and manipulating the balance between the SA and jasmonic acid defence pathway crosstalk.[27]

Enhance bioavailability and stability of active components:

The biopharmaceutical classification system categorizes drug and nutrients into four classes based on their solubility and permeability which dictates how a supplement must be designed to ensure its effective bioavailability and stability are key factors addressed by this system class 1 compounds absorb well because they dissolve and penetrate easily requiring little formulation effort class 2 compounds like fat-soluble vitamins A and D dissolve poorly but penetrate easily, so formulators must focus on improving dissolution by placing them in oil or special delivery system to ensure sufficient bioavailability.[28]

Reduce cytotoxicity through complementary effects:

When tackling any serious illness the main challenges isn’t just killing the disease, but making sure the treatment doesn’t cause too much collateral damage to the patient healthy body to lower this toxicity there are two primary clever approaches used firstly doctor often pair the main therapeutic agent with a protective compound a kind of molecules shield that specifically guards the good normal cells from the harsh side effects while leaving the primary drug free to attack the target.[29]

DELAY MICROBIAL ADAPTATION AND RESISTANCE DEVELOPMENT:

Most of what we currently know about how microbes like bacteria adjust and change in their natural environment comes from simply watching or comparing different groups and communities found in the wild. However, the actual detailed knowledge about how this adjustmental studies where the core process of adaptation is mostly learned from controlled experimental studies where scientists intentionally make microbes evolve under artificial test tube condition in a lab.[30]

Natural sources contain helpful compounds called antioxidants that keep us healthy by neutralizing harmful substance in the body called free radicals the primary goal of this research is to thoroughly check the antioxidant strength of various extracts by measuring exactly how much of the key active ingredients like phenolic, flavonoids, and alkaloids they-contain.[31]

CONCLUSION: